Metastatic Urothelial Carcinoma (mUC) Or Advanced Bladder Cancer Articles

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  • A Multicenter, Open-Label Phase 1b/2 Trial of Lenvatinib (E7080) Plus Pembrolizumab in Subjects With Selected Solid Tumors

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    A Multicenter, Open-Label Phase 1b/2 Trial of Lenvatinib (E7080) Plus Pembrolizumab in Subjects With Selected Solid Tumors


    Condition: Tumors

    Intervention:

    • Drug: Lenvatinib
    • Drug: Pembrolizumab

    Purpose: This is an open-label Phase 1b/2 trial of lenvatinib (E7080) plus pembrolizumab in participants with selected solid tumors. Phase 1b will determine and confirm the maximum tolerated dose (MTD) for lenvatinib in combination with 200 milligrams (mg) (intravenous [IV], every 3 weeks [Q3W]) pembrolizumab in participants with selected solid tumors (i.e. non-small cell lung cancer, renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma). Phase 2 (Expansion) will evaluate the safety and efficacy of the combination in 6 cohorts at the MTD from Phase 1b (lenvatinib 20 mg/day orally + pembrolizumab 200 mg Q3W, IV).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02501096

    Sponsor: Eisai Inc.

    Primary Outcome Measures:

    • Measure: MTD (Phase 1b)
    • Time Frame: Cycle 1 (21 Days)
    • Safety Issue:
    • Measure: Objective response rate (ORR) at Week 24
    • Time Frame: Week 24
    • Safety Issue:
    • Measure: Dose Limiting Toxicity (DLT) (Phase 1b)
    • Time Frame: Cycle 1 (21 Days)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Number of participants with treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (SAEs)
    • Time Frame: For each participant, from the first dose till 90 days after the last dose, unless participant starts new anticancer drug then 30 days, or up to approximately 2 years
    • Safety Issue:
    • Measure: ORR
    • Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years
    • Safety Issue:
    • Measure: Progression-free survival (PFS)
    • Time Frame: From the date of first dose of study drug to the date of first documentation of confirmed disease progression or death (whichever occurs first) or up to approximately 2 years
    • Safety Issue:
    • Measure: Overall survival (OS)
    • Time Frame: From the date of first dose of study drug until date of death from any cause or up to approximately 2 years
    • Safety Issue:
    • Measure: Duration of response (DOR)
    • Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years
    • Safety Issue:
    • Measure: Disease control rate (DCR)
    • Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years
    • Safety Issue:
    • Measure: Durable stable disease rate (DSDR)
    • Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years
    • Safety Issue:
    • Measure: Clinical benefit rate (CBR)
    • Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years
    • Safety Issue:
    • Measure: Area under the curve (AUC) of lenvatinib
    • Time Frame: 0.5-4 hours (hrs), and 6-10 hrs post lenvatinib dose on C1D1, pre-dose, 0.5-4 hrs, and 6-10 hrs post lenvatinib dose on C1D15, and pre-pembrolizumab dose and 2-12 hrs post lenvatinib dose on C2D1. Pre-pembrolizumab dose only on Day 1 of Cycles 3 to 6.
    • Safety Issue:
    • Measure: Apparent clearance of lenvatinib
    • Time Frame: 0.5-4 hours (hrs), and 6-10 hrs post lenvatinib dose on C1D1, pre-dose, 0.5-4 hrs, and 6-10 hrs post lenvatinib dose on C1D15, and pre-pembrolizumab dose and 2-12 hrs post lenvatinib dose on C2D1. Pre-pembrolizumab dose only on Day 1 of Cycles 3 to 6.
    • Safety Issue:

    Estimated Enrollment: 360

    Study Start Date: July 22, 2015

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Phase 1b: Histologically and/or cytologically confirmed metastatic selected solid tumor types that have progressed after treatment with approved therapies or for which there are no standard effective therapies available. If nivolumab or pembrolizumab is an approved therapy for the participant's tumor type, but the participant has not been treated with it, the Investigator may enroll the participant in this study. Phase 2: Histologically and/or cytologically confirmed metastatic selected solid tumor types with 0-2 prior lines of systemic therapy (unless discussed with the sponsor). For the non-small cell lung cancer (NSCLC) and melanoma cohorts, participants must have progressed on or after prior treatment with one anti-PD-1, anti-PD-L1, or anti-PDL2 agent. For the renal cell carcinoma (RCC) cohort, participants must have progressed on treatment with an anti- programmed death receptor-1 /programmed death receptor-ligand 1 monoclonal antibody (anti-PD-1/PD-L1 mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, the regimen with an anti-PD-1/PD-L1 mAb must be the most recent therapy. Selected tumor types of both phases: NSCLC, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma) 2. Life expectancy of 12 weeks or more 3. Phase 2: Measurable disease meeting the following criteria: 1. At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST (immune-related RECIST) using computerized tomography/magnetic resonance imaging (CT/MRI) 2. Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion 4. Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 5. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle 1 Day 1 6. Adequate renal function defined as creatinine less than or equal to 1.5 X ULN (upper limit of normal) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula with creatinine levels greater than 1.5 X ULN 7. Adequate bone marrow function: 1. Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/uL) 2. Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L) 3. Hemoglobin greater than or equal to 9.0 g/dL 8. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5 9. Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the ULN and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (in the case of liver metastases less than or equal to 5 X ULN). In case ALP is greater than 3 X ULN (in the absence of liver metastases) or greater than 5 X ULN (in the presence of liver metastases) AND the participant also is known to have bone metastases, the liver specific ALP must be separated from the total and used to assess the liver function instead of the total ALP 10. Males or females age greater than or equal to 18 years at the time of informed consent 11. Participants with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection) and if they have remained clinically stable, asymptomatic and off of steroids for at least 28 days before starting study treatment. 12. All females must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [β-hCG]) at the Screening Visit and the Baseline Visit. A pregnancy test needs to be performed within 72 hours of the first dose of study drug. Females of childbearing potential must agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation, ie
    • total abstinence (if it is their preferred and usual lifestyle)
    • an intrauterine device (IUD) or hormone-releasing system (IUS)
    • a contraceptive implant
    • an oral contraceptive** (with additional barrier method) OR
    • have a vasectomized partner with confirmed azoospermia. NOTES:
    • All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
    • Must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study 13. Male participants who are partners of women of childbearing potential must use a condom + spermicide and their female partners if of childbearing potential must use a highly effective method of contraception (see methods described in Inclusion Criterion #12) beginning at least 1 menstrual cycle prior to starting study drug(s), throughout the entire study period, and for 120 days after the last dose of study drug, unless the male participants are totally sexually abstinent or have undergone a successful vasectomy with confirmed azoospermia or unless the female partners have been sterilized surgically or are otherwise proven sterile. 14. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol 15. Archival tumor tissue or a newly obtained biopsy must be available prior to the first dose of study drug for biomarker analysis. In the case archival tissue cannot be provided, participants with inaccessible tumors for biopsy specimens can be enrolled without a biopsy upon consultation and agreement by the sponsor Note: In case of submitting unstained cut slides, freshly cut slides should be submitted to the testing laboratory within 14 days from when the slides are cut.

    Exclusion Criteria:

    1. Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter) or any investigational agent within 30 days prior to the first dose of study drugs. All acute toxicities related to prior treatments must be resolved to Grade less than or equal to 1
    2. Participants must have recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy
    3. Participants having greater than 1+ proteinuria on urinalysis will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein greater than or equal to 1 g/24-hour will be ineligible.
    4. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
    5. New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
    6. Prolongation of QTc interval to greater than 480 msec
    7. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
    8. Active infection (any infection requiring systemic treatment)
    9. Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
    10. Serious nonhealing wound, ulcer, or bone fracture
    11. Known intolerance to either of the study drugs (or any of the excipients)
    12. History of organ allograft (Participant has had an allogenic tissue/solid organ transplant)
    13. Biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before first dose of study treatment
    14. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
    15. Females who are pregnant or breastfeeding
    16. Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months
    17. Prior treatment with lenvatinib or any PD-1, anti-PD-L1, or anti-PD-L2 agent, excluding melanoma and NSCLC where prior treatment with one PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed, and excluding RCC where prior treatment with one regimen containing an anti-PD-1/PD-L1 mAb is required.
    18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5mg/d of prednisone or equivalent) may be approved after consultation with the sponsor.
    19. No active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    20. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
    21. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

    Contact:

    • Eisai Medical Information
    • 1-888-274-2378

    Locations:

    • Alaska Clinical Research Center
    • Anchorage Alaska United States
    • Arizona Oncology Associates
    • Oro Valley Arizona United States
    • Arizona Oncology Associates, PC - HOPE, Site #1
    • Tucson Arizona United States
    • Arizona Oncology Associates, PC - HOPE, Site #2
    • Tucson Arizona United States
    • Arizona Oncology Associates, PC - HOPE, Site #3
    • Tucson Arizona United States
    • Rocky Mountain Cancer Centers
    • Aurora Colorado United States
    • Rocky Mountain Cancer Centers
    • Boulder Colorado United States
    • Rocky Mountain Cancer Centers
    • Colorado Springs Colorado United States
    • Rocky Mountain Cancer Centers, Site #1
    • Denver Colorado United States
    • Rocky Mountain Cancer Centers, Site #2
    • Denver Colorado United States
    • Rocky Mountain Cancer Centers
    • Lakewood Colorado United States
    • Rocky Mountain Cancer Centers
    • Littleton Colorado United States
    • Rocky Mountain Cancer Centers
    • Lone Tree Colorado United States
    • Rocky Mountain Cancer Centers
    • Longmont Colorado United States
    • Rocky Mountain Cancer Centers
    • Parker Colorado United States
    • Rocky Mountain Cancer Centers
    • Pueblo Colorado United States
    • Rocky Mountain Cancer Centers
    • Thornton Colorado United States
    • Baptist Health Medical Group Oncology, LLC, Site #1
    • Miami Florida United States
    • Baptist Health Medical Group Oncology, LLC, Site #2
    • Miami Florida United States
    • Baptist Health Medical Group Oncology, LLC, Site #3
    • Miami Florida United States
    • Boca Raton Clinical Research Medical Center
    • Plantation Florida United States
    • Piedmont Cancer Institue
    • Atlanta Georgia United States
    • Rush University Medical
    • Chicago Illinois 60612 United States
    • The University of Chicago
    • Chicago Illinois United States
    • Beth Israel Deaconess Medical Center
    • Boston Massachusetts United States
    • Mass General Hospital
    • Boston Massachusetts United States
    • University of Minnesota, Masonic Cancer Center
    • Minneapolis Minnesota United States
    • Comprehensive Cancer Centers of Nevada, Site #1
    • Henderson Nevada United States
    • Comprehensive Cancer Centers of Nevada, Site #2
    • Henderson Nevada United States
    • Comprehensive Cancer Centers of Nevada, Site #3
    • Henderson Nevada United States
    • Comprehensive Cancer Centers of Nevada, Site #1
    • Las Vegas Nevada United States
    • Comprehensive Cancer Centers of Nevada, Site #2
    • Las Vegas Nevada United States
    • Comprehensive Cancer Centers of Nevada, Site #3
    • Las Vegas Nevada United States
    • Comprehensive Cancer Centers of Nevada, Site #4
    • Las Vegas Nevada United States
    • New York Hematology Oncology (US Onc)
    • Albany New York United States
    • Memorial Sloan Kettering at Westchester
    • Harrison New York United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York United States
    • Oregon Health & Science University
    • Portland Oregon United States
    • University of Pennsylvania
    • Philadelphia Pennsylvania United States
    • Greenville Health System
    • Easley South Carolina United States
    • Greenville Health System, Site #1
    • Greenville South Carolina United States
    • Greenville Health System, Site #2
    • Greenville South Carolina United States
    • Greenville Health System, Site #3
    • Greenville South Carolina United States
    • Greenville Health System
    • Greer South Carolina United States
    • Greenville Health System
    • Seneca South Carolina United States
    • Greenville Health System
    • Spartanburg South Carolina United States
    • Texas Oncology-Bedford
    • Bedford Texas United States
    • Texas Oncology (US Onc)
    • Dallas Texas United States
    • Texas Oncology
    • Dallas Texas United States
    • Texas Oncology-Denton South
    • Denton Texas United States
    • Texas Oncology-Fort Worth, Site #1
    • Fort Worth Texas United States
    • Texas Oncology-Fort Worth, Site #2
    • Fort Worth Texas United States
    • Texas Oncology-Garland
    • Garland Texas United States
    • Texas Oncology-Grapevine
    • Grapevine Texas United States
    • Texas Oncology-Longview Cancer Center
    • Longview Texas United States
    • Texas Oncology-Plano West
    • Plano Texas United States
    • South Texas Accelerated Research Therapeutics, LLC
    • San Antonio Texas United States
    • US Oncology Network
    • The Woodlands Texas United States
    • Texas Oncology-Tyler
    • Tyler Texas United States
    • Texas Oncology-Waco, Site #1
    • Waco Texas United States
    • Texas Oncology-Waco, Site #2
    • Waco Texas United States
    • Haukeland Univerity Hospital
    • Bergen Norway
    • Sørlandet Hospital
    • Kristiansand 4604 Norway
    • Akershus Universitetssykehus HF
    • Lørenskog Norway
    • Oslo Univerity Hospital
    • Oslo Norway
    • Sykehuset Østfold
    • Sarpsborg Norway
    • Hospital Universitari Germans Trias i Pujol
    • Badalona Spain
    • Hospital Universitari Vall d'Hebron
    • Barcelona Spain
    • Hospital Universitario De Fuenlabrada
    • Fuenlabrada Spain
    • Hospital La Paz
    • Madrid Spain
    • Hospital Universitario Clinico San Carlos
    • Madrid Spain
    • MD Anderson Cancer Center Madrid - España
    • Madrid Spain
    • Parc Taulí Sabadell
    • Sabadell Spain
    • Hospital Virgen de la Salud
    • Toledo Spain
    • Hospital Universitari i Politécnic La Fe.
    • Valencia Spain

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

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    A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer


    Condition: Metastatic Urothelial Cancer

    Intervention:

    • Drug: AGS15E

    Purpose: The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01963052

    Sponsor: Agensys, Inc.

    Primary Outcome Measures:

    • Measure: Incidence of adverse events
    • Time Frame: up to 36 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)
    • Time Frame: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence of Anti-Drug Antibody (ADA)
    • Time Frame: Up to 26 months
    • Safety Issue:
    • Measure: Tumor response
    • Time Frame: Up to 26 months
    • Safety Issue:
    • Measure: Objective response rate
    • Time Frame: Up to 26 months
    • Safety Issue:
    • Measure: Disease control rate
    • Time Frame: Up to 26 months
    • Safety Issue:
    • Measure: Progression free survival
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Duration of response
    • Time Frame: Up to 36 months
    • Safety Issue:

    Estimated Enrollment: 93

    Study Start Date: November 14, 2013

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
    • Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.
    • Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).
    • Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting
    • Subjects must have measureable disease according to RECIST (version 1.1).
    • Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    • Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
    • Life expectancy of ≥ 3 months
    • Adequate hematologic function
    • Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min
    • Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and <60 mL/min by cockroft gault equation adjusted for body weight
    • Adequate liver function

    Exclusion Criteria:

    • Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2
    • Uncontrolled central nervous system metastases
    • Use of any investigational drug within 14 days prior to the first dose of study drug
    • Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
    • Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible
    • Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug
    • History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
    • Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
    • Known HIV or AIDS
    • Positive Hepatitis B surface antigen test
    • Positive Hepatitis C antibody test
    • Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
    • Known sensitivity to any of the ingredients of the investigational product AGS15E
    • Major surgery within 28 days prior to first dose of study drug
    • History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:
    • Non-melanoma skin cancer;
    • adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable;
    • cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and
    • definitively treated, stage I/II ER+ breast cancer
    • Active infection requiring treatment ≤ 7 days before first dose of study drug
    • History of uncontrolled diabetes mellitus or diabetic neuropathy
    • Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
    • Has ocular conditions such as:
    • Active infection or corneal ulcer (e.g., keratitis)
    • Monocularity
    • History of corneal transplantation
    • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
    • Uncontrolled glaucoma (topical medications allowed)
    • Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder

    Locations:

    • Site US00006
    • Birmingham Alabama 35294 United States
    • Site US00002
    • New Haven Connecticut 06510 United States
    • Site US00001
    • Detroit Michigan 48201 United States
    • Site US00003
    • Saint Louis Missouri 63110 United States
    • Site US00009
    • Buffalo New York 14263 United States
    • Site US00010
    • Nashville Tennessee 37212 United States
    • Site US00008
    • Seattle Washington 98109 United States
    • Site CA00004
    • Vancouver British Columbia V5Z 1H5 Canada
    • Site CA00007
    • Hamilton Ontario L8V 5C2 Canada
    • Site CA00005
    • Toronto Ontario M4N 3M5 Canada

    View trial on ClinicalTrials.gov


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    Published July 29, 2017
  • A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

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    A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4


    Condition: Metastatic Urothelial Cancer and Other Malignant Solid Tumors

    Intervention:

    • Drug: enfortumab vedotin

    Purpose: The purpose of this study is to evaluate the safety and pharmacokinetics of enfortumab vedotin as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors that express Nectin-4.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02091999

    Sponsor: Astellas Pharma Global Development, Inc.

    Primary Outcome Measures:

    • Measure: Incidence of adverse events
    • Time Frame: up to 36 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:
    • Measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)
    • Time Frame: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence of Anti-Drug Antibody (ADA)
    • Time Frame: up to 24 months
    • Safety Issue:
    • Measure: Tumor response
    • Time Frame: up to 24 months
    • Safety Issue:
    • Measure: Objective response rate
    • Time Frame: up to 24 months
    • Safety Issue:
    • Measure: Disease control rate
    • Time Frame: up to 24 months
    • Safety Issue:
    • Measure: Progression Free Survival (PFS)
    • Time Frame: 36 months
    • Safety Issue:
    • Measure: Overall Survival
    • Time Frame: 36 months
    • Safety Issue:
    • Measure: Duration of Response
    • Time Frame: 36 months
    • Safety Issue:

    Estimated Enrollment: 215

    Study Start Date: June 4, 2014

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Dose Escalation, Renal insufficiency and CPI-Treated Expansion cohorts: Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
    • Ovarian Expansion Cohort: Subjects with recurrent disease or histologically or cytologically confirmed Stage III/IV diagnosis of epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma who have previously progressed while receiving or within 6 months of completing a platinum-containing regimen.
    • NSCLC Expansion Cohort: Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)
    • Dose Escalation, Renal insufficiency, NSCLC and CPI-Treated Expansion Cohorts: For subjects with urothelial cancer and NSCLC: Subjects must submit a tumor tissue for Nectin-4 expression. Enrollment for these subjects is not dependent on the immunohistochemistry using the H-Score (IHC H-Score).
    • Ovarian Expansion Cohort: Subjects must have tumor tissue positive (IHC H-score ≥150) for Nectin-4 expression
    • For Dose Escalation, NSCLC and Ovarian Expansion Cohorts: Subject must have failed at least one prior chemotherapy regimen for metastatic disease (urothelial and bladder cancer subjects are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy)
    • For the CPI-Treated Expansion Cohort: Subject must have received prior treatment with a CPI in the metastatic setting.
    • Subjects must have measurable disease according to RECIST (version 1.1)
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    • Life expectancy of ≥ 3 months
    • Negative pregnancy test (women of childbearing potential)
    • Hematologic function, as follows (no red blood cell or platelet transfusions are allowed within 14 days of the first dose of enfortumab vedotin):
    • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
    • Platelet count ≥ 100 x 10^9/L
    • Hemoglobin ≥ 9 g/dL
    • Renal function, as follows: Dose Escalation, NSCLC, Ovarian, and CPI Treated Expansion Cohorts: creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation or as measured by 24 hour urine collection. For the Renal Insufficiency Expansion Cohort: creatinine clearance estimate ≥15 ml/min and <30 ml/min by Cockcroft-Gault equation or as measured by 24 hour urine collection.
    • Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
    • Serum albumin ≥2.5 g/dL
    • Aspartate aminotransferase (AST) ≤ 1.5 x ULN
    • Alanine aminotransferase (ALT) ≤ 1.5 x ULN
    • International normal ratio (INR) < 1.3 or ≤ institutional ULN (or ≤ 3.0 if on therapeutic anticoagulation)
    • Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 months after termination of study therapy
    • Competent to comprehend, sign, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form

    Exclusion Criteria:

    • Preexisting sensory neuropathy Grade ≥ 2
    • Preexisting motor neuropathy Grade ≥ 2
    • Uncontrolled central nervous system metastases
    • Use of any investigational drug within 14 days prior to the first dose of study drug
    • Any anticancer therapy within 14 days prior to the first dose of study drug, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
    • Subjects with immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible.
    • Any P-glycoprotein (P-gp) inducers/inhibitors or strong cytochrome P4503A (CYP3A) inhibitors within 14 days prior to the first dose of study drug
    • Thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
    • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of enfortumab vedotin.
    • Known Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS)
    • Subjects with a positive Hepatitis B surface antigen and/or antihepatitis B core antibody. Subjects with a negative polymerase chain reaction (PCR) assay are permitted with appropriate antiviral prophylaxis.
    • Active Hepatitis C infection. Subjects who have been treated for Hepatitis C infection can be included if they have documented sustained virologic response of ≥ 12 weeks.
    • Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
    • Known sensitivity to any of the ingredients of the investigational product enfortumab vedotin (ASG-22CE)
    • Major surgery within 28 days prior to first dose of study drug
    • History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low risk localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any time (if complete resection was performed) are allowed.
    • History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months of the first dose of study drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c > 7 to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
    • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
    • Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
    • Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
    • Has ocular conditions such as:
    • Active infection or corneal ulcer (e.g. keratitis)
    • Monocularity
    • History of corneal transplantation
    • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
    • Uncontrolled glaucoma (topical medications allowed)
    • Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder

    Contact:

    • Astellas Pharma Global Development
    • 800-888-7704

    Locations:

    • Site US00012
    • Los Angeles California 90033 United States
    • Site US00019
    • Stanford California 94305 United States
    • Site US00017
    • Aurora Colorado 80045 United States
    • Site US00006
    • New Haven Connecticut 06520 United States
    • Site US00007
    • Miami Florida 33136 United States
    • Site US00008
    • Tampa Florida 33612 United States
    • Site US00027
    • Harvey Illinois 60426 United States
    • Site US00016
    • Indianapolis Indiana 46202 United States
    • Site US00004
    • Fairway Kansas 66205 United States
    • Site US00014
    • Baltimore Maryland 21201 United States
    • Site US00005
    • Ann Arbor Michigan 48109 United States
    • Site US00003
    • Detroit Michigan 48201 United States
    • Site US00026
    • Omaha Nebraska 68130 United States
    • Site US00021
    • Las Vegas Nevada 89119 United States
    • Site US00018
    • New York New York 10029 United States
    • Site US00002
    • New York New York 10065 United States
    • Site US00023
    • Chapel Hill North Carolina 27599 United States
    • Site US00013
    • Philadelphia Pennsylvania 19111 United States
    • Site US00020
    • Pittsburgh Pennsylvania 15232 United States
    • Site US00022
    • Dallas Texas 75251 United States
    • Site US00024
    • Fairfax Virginia 22031 United States
    • Site US00001
    • Seattle Washington 98109 United States
    • Site US00025
    • Spokane Washington 99208 United States
    • Site US00009
    • Madison Wisconsin 53792 United States
    • Site US00015
    • Milwaukee Wisconsin 53226 United States
    • Site CA00011
    • Calgary Alberta T2N 4N2 Canada
    • Site CA00001
    • Edmonton Alberta T6G 1Z2 Canada
    • Site CA00010
    • Toronto Ontario M5G 2M9 Canada

    View trial on ClinicalTrials.gov


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    Published June 6, 2017
  • A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors

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    A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors


    Condition: HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Bladder Cancer, HER2-positive Solid Tumor

    Intervention:

    • Drug: PRS-343

    Purpose: A multi center, open-label, Phase 1 dose escalation study with expansion cohort is designed to determine the MTD, RP2D and dosing schedule of PRS-343 in patients with HER2+ advanced or metastatic solid tumors.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03330561

    Sponsor: Pieris Pharmaceuticals, Inc.

    Primary Outcome Measures:

    • Measure: Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4
    • Time Frame: Up to 36 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Peak Plasma Concentration (Cmax)
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Area under the plasma concentration versus time curve (AUC)
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Time to maximum dose concentration (Tmax)
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Terminal half life (t1/2)
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Tumor responses as defined by the Response Evaluation in Solid Tumors (RECIST) v.1.1
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Duration of response
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Disease control rate
    • Time Frame: Up to 36 months
    • Safety Issue:

    Estimated Enrollment: 78

    Study Start Date: September 28, 2017

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Signed written informed consent obtained prior to performing any study procedure, including pre-screening and screening procedures.
    2. Men and women ≥18 years.
    3. Dose escalation: Histologically or cytologically confirmed diagnosis of unresectable/locally advanced and/or metastatic HER2+ solid tumor malignancy and for which standard therapies are not available, are no longer effective, are not tolerated, or have been declined by the patient. Expansion cohort: Locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2-targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder).
    4. Dose escalation and expansion cohort: HER2+ tumors documented by clinical pathology report:
    5. Assessment of HER2 status in patients with breast cancer should follow the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria (37) as practicable.
    6. Assessment of HER2 status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. (38) as practicable.
    7. Assessment of HER2 status in patients with non-breast/non-gastric cancers may follow local institutional criteria. These criteria should be made available to the Sponsor.
    8. All patients with breast and gastric/gastroesophageal junction cancers should have HER2 testing performed using a FDA approved test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
    9. Patients for whom the clinical pathology report includes only IHC as 3+ (does not reflex to ISH) may enroll without written report of ISH determined HER2 copy number, provided the investigational site confirms that archival tissue is available.
    10. Patients with breast cancer and gastric and gastroesophageal junction cancer must have received at least 1 prior HER2 targeted therapy for advanced/metastatic disease.
    11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
    12. Estimated life expectancy of at least 3 months.
    13. Dose Escalation: Evaluable or measurable disease according to RECIST v1.1 Expansion Cohort (additional 30 patients) Measurable disease according to RECIST v1.
    14. Adequate organ function as defined below:
    15. Serum AST and ALT ≤ 3 X ULN
    16. Total serum bilirubin ≤ 1.5 X ULN
    17. Serum creatinine ≤ 1.5 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 50 mL/min
    18. Hemoglobin ≥ 9 g/dL
    19. ANC ≥ 1500/mm3
    20. Platelet count ≥ 75,000/mm3
    21. Left ventricular ejection fraction (LVEF) determined by echocardiogram or multi-gated acquisition scan ≥ 50%
    22. Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m
    23. Women of childbearing potential must have a negative serum or urine pregnancy test within 96 hours prior to start of study drug.
    24. Women must not be breastfeeding.
    25. Women of childbearing potential must agree to follow instruction for method(s) of contraception for the duration of treatment with study drug PRS-343 plus 90 days post-treatment completion.
    26. Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug PRS 343 plus 90 days post-treatment completion.

    Exclusion Criteria:

    1. Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
    2. History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks.
    3. History of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Appendix B).
    4. History of ejection fraction drop below the lower limit of normal with trastuzumab and/or pertuzumab.
    5. Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study.
    6. Any severe concurrent disease or condition (includes active infections, cardiac arrhythmia, interstitial lung disease) that in the judgment of the investigator would make study participation inappropriate for the patient.
    7. Previously known infection with human immunodeficiency virus (HIV); or hepatitis B or hepatitis C infection.
    8. History of infusion reactions to any component/excipient of PRS-3
    9. Systemic steroid therapy (>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment (Note: topical, inhaled, nasal and ophthalmic steroids are not prohibited).
    10. Autoimmune disease that has required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
    11. Has not recovered from the adverse effect of previous anticancer treatments to pre-treatment baseline or Grade 1 except for alopecia, anemia (hemoglobin must meet the study inclusion criteria) and peripheral neuropathy (which must have recovered to ≤ Grade 2).
    12. History of a second primary cancer with the exception of 1) curatively treated non-melanomatous skin cancer, 2) curatively treated cervical or breast carcinoma in situ, or 3) other malignancy with no known active disease present and no treatment administered during the last 2 years.
    13. Receipt of investigational treatment within 3 weeks of scheduled Cycle 1 Day 1 (C1D1) dosing.
    14. Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled C1D1 dosing.
    15. Receipt of radiation therapy within 3 weeks of scheduled C1D1 dosing, unless the radiation comprised a limited field to non-visceral structures (e.g., limb bone metastasis).
    16. Receipt of treatment with immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled C1D1 dosing.
    17. Receipt of trastuzumab or ado-trastuzumab emtansine within 4 weeks of scheduled C1D1 dosing.
    18. Concurrent enrollment in another therapeutic clinical trial.
    19. Major surgery within 3 weeks of scheduled C1D1 dosing.

    Contact:

    • Ingmar Bruns, MD PhD
    • +1-857-246-8998

    Locations:

    • University of Arizona Cancer Center
    • Tucson Arizona 85719 United States
    • University of California Los Angeles (UCLA)
    • Santa Monica California 90404 United States
    • Georgetown University, Lombardi Comprehensive Cancer Center
    • Washington District of Columbia 20007 United States
    • Johns Hopkins University School of Medicine
    • Baltimore Maryland 21287 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10065 United States
    • University of Pittsburgh Medical Center (UPMC)
    • Pittsburgh Pennsylvania 15213 United States
    • Sarah Cannon Research Institute
    • Nashville Tennessee 37203 United States
    • M.D. Anderson Cancer Center
    • Houston Texas 77030 United States
    • START - South Texas Accelerated Research Therapeutics, LLC
    • San Antonio Texas 78229 United States
    • NEXT Oncology
    • San Antonio Texas 78240 United States

    View trial on ClinicalTrials.gov


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    Published September 16, 2019
  • A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)

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    A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)


    Condition: Solid Tumors, Head and Neck Cancer, Lung Cancer, UC (Urothelial Cancer)

    Intervention:

    • Drug: MEDI4736
    • Drug: INCB024360

    Purpose: The purpose of this study is to explore the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of INCB024360 administered in combination with MEDI4736 in subjects with selected advanced solid tumors.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02318277

    Sponsor: Incyte Corporation

    Primary Outcome Measures:

    • Measure: Phase 1: Incidence of Dose Limiting Toxicities and frequency, duration, and severity of Adverse Events (AEs)
    • Time Frame: Duration of study treatment and up to 90 days after the last dose [approximately 9 months]
    • Safety Issue:
    • Measure: Phase 2: Objective Response Rate (ORR) as determined by radiographic disease assessments per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
    • Time Frame: Measured every 8 weeks for duration of study treatment [approximately 6 months]
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Phase 1: Objective Response Rate (ORR) as determined by radiographic disease assessments per modified RECIST v1.1
    • Time Frame: Measured every 8 weeks for duration of study treatment [approximately 6 months]
    • Safety Issue:
    • Measure: Phase 2: Frequency, duration, and severity of AEs
    • Time Frame: Continuously for duration of study treatment and up to 90 days after the last dose
    • Safety Issue:
    • Measure: Phase 1 and 2: Durability of response as measured by the time from the earliest date of disease response until earliest date of disease progression
    • Time Frame: Measured every 8 weeks for duration of active study treatment [approximately 6 months]
    • Safety Issue:
    • Measure: Phase 1 and 2: Progression-free survival as measured by the duration from the date of enrollment until the earliest date of disease progression or death
    • Time Frame: Measured every 8 weeks for duration of active study treatment [approximately 6 months]
    • Safety Issue:
    • Measure: Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 and MEDI4736 as measured by peak concentration
    • Time Frame: Measured at defined study visits from Cycle 1 Day 1 through 90 days after the last dose of MEDI4736 [approximately 9 months]
    • Safety Issue:
    • Measure: Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 and MEDI4736 as measured by time to maximal observed concentration
    • Time Frame: Measured at defined study visits from Cycle 1 Day 1 through 90 days after the last dose of MEDI4736 [approximately 9 months]
    • Safety Issue:
    • Measure: Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 and MEDI4736 as area under the concentration-time curve
    • Time Frame: Measured at defined study visits from Cycle 1 Day 1 through 90 days after the last dose of MEDI4736 [approximately 9 months]
    • Safety Issue:
    • Measure: Phase 1 and 2: Immunogenicity of MEDI4736 as measured by the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)
    • Time Frame: Measured at defined study visits from Cycle 1 Day 1 through 90 days after the last dose of MEDI4736 [approximately 9 months]
    • Safety Issue:

    Estimated Enrollment: 192

    Study Start Date: December 2014

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Male or female subjects, age 18 years or older
    • Histologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumors
    • Must have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment

    Exclusion Criteria:

    • Laboratory and medical history parameters not within protocol-defined range
    • Participation in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose
    • Prior treatment with immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell co-stimulation) or an IDO inhibitor (exception is tumor types in which a PD-1 pathway targeted agent is approved, e.g. melanoma, non-small cell lung cancer.)
    • Receipt of any anticancer medication in the 21 days prior to receiving the first dose of study medication
    • Has an active or inactive autoimmune process
    • Evidence of interstitial lung disease or active, non-infectious pneumonitis
    • Prior radiotherapy within 2 weeks of initiating treatment; Must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
    • Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
    • Currently pregnant or breastfeeding

    Contact:

    • Incyte Corporation Call Center (US)
    • 1.855.463.3463

    Locations:

    • San Francisco California United States
    • Denver Colorado United States
    • Miami Florida United States
    • Port Saint Lucie Florida United States
    • Sarasota Florida United States
    • Tampa Florida United States
    • Chicago Illinois United States
    • Louisville Kentucky United States
    • Durham North Carolina United States
    • Huntersville North Carolina United States
    • Winston-Salem North Carolina United States
    • Dallas Texas United States
    • Houston Texas United States

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • A Phase 1b Dose-escalation and Dose-expansion Study of Enfortumab Vedotin (ASG-22CE) in Combination With Immune Checkpoint Inhibitor (CPI) Therapy for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer

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    A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer


    Condition: Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms, Renal Pelvis Neoplasms, Urothelial Cancer, Ureteral Neoplasms, Urethral Neoplasms

    Intervention:

    • Drug: enfortumab vedotin
    • Drug: pembrolizumab
    • Drug: cisplatin
    • Drug: carboplatin
    • Drug: gemcitabine

    Purpose: This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to treat patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of the study will look at locally-advanced and metastatic urothelial cancer, which means the cancer has spread to nearby tissues or to other areas of the body. Other parts of the study will look at muscle-invasive urothelial cancer, which is cancer at an earlier stage that has spread into the muscle wall of the bladder. This study will look at the side effects of enfortumab vedotin alone and with other anticancer therapies. A side effect is a response to a drug that is not part of the treatment effect. This study will also test if the cancer shrinks with the different treatment combinations.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03288545

    Sponsor: Astellas Pharma Global Development, Inc.

    Primary Outcome Measures:

    • Measure: Type, incidence, severity, seriousness, and relatedness of adverse events (locally advanced/metastatic urothelial cancer [la/mUC] cohorts only)
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
    • Safety Issue:
    • Measure: Type, incidence, and severity of laboratory abnormalities (la/mUC cohorts only)
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
    • Safety Issue:
    • Measure: Pathological complete response (pCR) rate per local pathology review (muscle invasive urothelial cancer [MIUC] cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence of dose-limiting toxicity (DLT)
    • Time Frame: 21 days
    • Safety Issue:
    • Measure: Confirmed objective response rate (ORR) by investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (la/mUC cohorts only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Confirmed ORR per the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (la/mUC cohorts using pembrolizumab only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: DCR by investigator assessment according to iRECIST 1.1 (la/mUC cohorts using pembrolizumab only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: DOR by investigator assessment according to iRECIST 1.1 (la/mUC cohorts using pembrolizumab only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Progression free survival (PFS) by investigator assessment according to RECIST 1.1 (all cohorts)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: PFS by investigator assessment according to iRECIST 1.1 (la/mUC cohorts using pembrolizumab only)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Overall survival (OS) (all cohorts)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (la/mUC cohorts only)
    • Time Frame: Through 2 cycles of treatment, up to 42 days
    • Safety Issue:
    • Measure: PK parameter for monomethyl auristatin E (MMAE): Cmax (la/mUC cohorts only)
    • Time Frame: Through 2 cycles of treatment, up to 42 days
    • Safety Issue:
    • Measure: PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (la/mUC cohorts only)
    • Time Frame: Through 2 cycles of treatment, up to 42 days
    • Safety Issue:
    • Measure: PK parameter for MMAE: Tmax (la/mUC cohorts only)
    • Time Frame: Through 2 cycles of treatment, up to 42 days
    • Safety Issue:
    • Measure: PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) (la/mUC cohorts only)
    • Time Frame: Through 2 cycles of treatment, up to 42 days
    • Safety Issue:
    • Measure: PK parameter for MMAE: AUC (la/mUC cohorts only)
    • Time Frame: Through 2 cycles of treatment, up to 42 days
    • Safety Issue:
    • Measure: Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (la/mUC cohorts only)
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
    • Safety Issue:
    • Measure: pCR rate per central pathology review (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:
    • Measure: Pathological response (PaR) rate per central pathology review (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:
    • Measure: PaR rate per local pathology review (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:
    • Measure: Disease-free survival (DFS) by investigator assessment according to RECIST 1.1 (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:
    • Measure: Type, incidence, severity, seriousness, and relatedness of AEs (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:
    • Measure: Type, incidence, and severity of laboratory abnormalities (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:
    • Measure: Percentage of planned surgeries delayed due to treatment-related AEs (MIUC cohorts only)
    • Time Frame: Up to approximately 5 months
    • Safety Issue:

    Estimated Enrollment: 257

    Study Start Date: October 11, 2017

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Locally advanced or metastatic urothelial (la/mUC)
    • Cohorts A, B, D, E, F, and G
    • Histologically documented la/mUC, including squamous differentiation or mixed cell types.
    • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2.
    • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, and G).
    • Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
    • Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
    • Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
    • Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Muscle Invasive Urothelial Cancer (MIUC)
    • Cohorts H and J
    • Histologically confirmed muscle invasive urothelial cancer of the bladder at clinical stage cT2-T4a.
    • Medically fit (i.e. eligible for surgery) and scheduled for radical cystectomy.
    • ECOG performance status of 0, 1, or 2.
    • Cohort H and J: Ineligible for cisplatin-based chemotherapy and no prior systemic treatment, chemoradiation, or radiation therapy for MIUC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-muscle invasive urothelial cancer.
    • Cohort J: Eligible for pembrolizumab.

    Exclusion Criteria:

    • la/mUC
    • Cohorts A, B, D, E, F, and G
    • Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
    • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
    • Ongoing sensory or motor neuropathy Grade 2 or higher.
    • Active central nervous system (CNS) metastases.
    • Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
    • Conditions requiring high doses of steroids or other immunosuppressive medications.
    • Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
    • Uncontrolled diabetes mellitus.
    • MIUC
    • Cohorts H and J
    • Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive urothelial cancer.
    • Received any prior treatment with a CPI.
    • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
    • Evidence of measurable nodal or metastatic disease.
    • Ongoing sensory or motor neuropathy Grade 2 or higher.
    • Conditions requiring high doses of steroids or other immunosuppressive medications.
    • Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
    • History of another malignancy within 3 years before first dose of study drug.

    Contact:

    • Seattle Genetics Trial Information Support
    • 866-333-7436

    Locations:

    • Alaska Urological Institute
    • Anchorage Alaska 99503 United States
    • Banner MD Anderson Cancer Center
    • Gilbert Arizona 85234 United States
    • Highlands Oncology Group
    • Fayetteville Arkansas 72703 United States
    • UC San Diego / Moores Cancer Center
    • La Jolla California 92093 United States
    • University of California Irvine - Newport
    • Orange California 92868 United States
    • University of California at San Francisco
    • San Francisco California 94134 United States
    • Stanford Cancer Center / Blood & Marrow Transplant Program
    • Stanford California 94305 United States
    • University of Colorado Hospital / University of Colorado
    • Aurora Colorado 80045-0510 United States
    • Yale Cancer Center
    • New Haven Connecticut 06520 United States
    • University of Miami
    • Miami Florida 33136 United States
    • Winship Cancer Institute / Emory University School of Medicine
    • Atlanta Georgia 30322 United States
    • Decatur Memorial Hospital - Illinois
    • Decatur Illinois 62526 United States
    • Cardinal Bernardin Cancer Center / Loyola University Medical Center
    • Maywood Illinois 60153 United States
    • University of Kansas Cancer Center
    • Westwood Kansas 66205 United States
    • Tulane University Hospital and Clinic
    • New Orleans Louisiana 70112 United States
    • University of Michigan Comprehensive Cancer Center
    • Ann Arbor Michigan 48109 United States
    • University of Minnesota
    • Minneapolis Minnesota 55455 United States
    • Hackensack University Medical Center
    • Hackensack New Jersey 07601 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • New York University (NYU) Cancer Institute
    • New York New York 10016 United States
    • Weill Cornell Medical College
    • New York New York 10065 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10087-9049 United States
    • UNC Lineberger Comprehensive Cancer Center / University of North Carolina
    • Chapel Hill North Carolina 27599 United States
    • Levine Cancer Institute
    • Charlotte North Carolina 28204 United States
    • Case Western Reserve University / University Hospitals Case Medical Center
    • Cleveland Ohio 44106 United States
    • Medical University of South Carolina/Hollings Cancer Center
    • Charleston South Carolina 29425 United States
    • Medical College of Wisconsin (Milwaukee)
    • Milwaukee Wisconsin 53226 United States

    View trial on ClinicalTrials.gov


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    Published January 29, 2018
  • A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

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    A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors


    Condition: Urothelial Carcinoma, Renal Cell Carcinoma, Non-Small Cell Lung Cancer, Castration-resistant Prostate Cancer, Triple Negative Breast Cancer, Ovarian Cancer, Endometrial Cancer, Hepatocellular Carcinoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Colorectal Cancer, Head and Neck Cancer, Differentiated Thyroid Cancer, Lower Esophageal Cancer

    Intervention:

    • Drug: cabozantinib
    • Drug: atezolizumab
    • Drug: cabozantinib
    • Drug: cabozantinib

    Purpose: This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric cancer/gastroesophageal junction cancer/lower esophageal cancer (GC/GEJC/LEC), colorectal cancer (CRC), head and neck (H&N) cancer, and differentiated thyroid cancer (DTC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy of the combination treatment in these tumor indications. Three exploratory single-agent cabozantinib (SAC) cohorts may also be enrolled with UC, NSCLC, or CRPC subjects. One exploratory single-agent atezolizumab (SAA) cohort may also be enrolled with CRPC subjects. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03170960

    Sponsor: Exelixis

    Primary Outcome Measures:

    • Measure: Dose Escalation: MTD/Recommended Dose
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: Dose Expansion: ORR
    • Time Frame: Up to 31 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence and severity of nonserious AEs and SAEs (Safety)
    • Time Frame: Up to 41 months
    • Safety Issue:

    Estimated Enrollment: 1732

    Study Start Date: September 5, 2017

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:
    • Dose-Escalation Stage:
    • Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
    • Subjects with RCC (clear cell, non-clear cell histology) with or without prior systemic anticancer therapy
    • Expansion Stage:
    • Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N cancer, and DTC as outlined above) 2. Measurable disease per RECIST 1.1 as determined by the investigator. 3. Tumor tissue material available (archival or recent tumor biopsy) 4. Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. 5. Age eighteen years or older on the day of consent. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 7. Adequate organ and marrow function. 8. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception. 9. Female subjects of childbearing potential must not be pregnant at screening.

    Exclusion Criteria:

    1. Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts 5, 7, 9, 11, 17, 19 and
    2. Other restrictions regarding prior therapy may apply.
    3. Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment.
    4. Concomitant anticoagulation with oral anticoagulants.
    5. Subject is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
    6. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
    7. The subject has uncontrolled, significant intercurrent or recent illness, including, but not limited to, an active or history of autoimmune disease or immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C).
    8. Pregnant or lactating females.
    9. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
    10. Diagnosis of another malignancy within 2 years before first dose of study treatment.

    Contact:

    • Exelixis Clinical Trials
    • 1-888-EXELIXIS (888-393-5494)

    Locations:

    • Exelixis Clinical Site #53
    • Gilbert Arizona 85234 United States
    • Exelixis Clinical Site #18
    • Phoenix Arizona 85054 United States
    • Exelixis Clinical Site #1
    • Duarte California 91010 United States
    • Exelixis Clinical Site #20
    • La Jolla California 92090 United States
    • Exelixis Clinical Site #46
    • Los Angeles California 90025 United States
    • Exelixis Clinical Site #51
    • Newport Beach California 92663 United States
    • Exelixis Clinical Site #21
    • Stanford California 94305 United States
    • Exelixis Clinical Site #34
    • Denver Colorado 80218 United States
    • Exelixis Clinical Site #50
    • Denver Colorado 80218 United States
    • Exelixis Clinical Site #42
    • New Haven Connecticut 06511 United States
    • Exelixis Clinical Site #48
    • Washington District of Columbia 20007 United States
    • Exelixis Clinical Site #16
    • Jacksonville Florida 32224 United States
    • Exelixis Clinical Site #32
    • Harvey Illinois 60426 United States
    • Exelixis Clinical Site #23
    • Fairway Kansas 66205 United States
    • Exelixis Clinical Site #57
    • Lexington Kentucky 40536 United States
    • Exelixis Clinical Site #24
    • New Orleans Louisiana 70112 United States
    • Exelixis Clinical Site #10
    • Boston Massachusetts 02215 United States
    • Exelixis Clinical Site #3
    • Detroit Michigan 48201 United States
    • Exelixis Clinical Site #17
    • Rochester Minnesota 55905 United States
    • Exelixis Clinical Site #43
    • Kansas City Missouri 64111 United States
    • Exelixis Clinical Site #35
    • Omaha Nebraska 68130 United States
    • Exelixis Clinical Site #38
    • Camden New Jersey 08103 United States
    • Exelixis Clinical Site #27
    • East Brunswick New Jersey 08816 United States
    • Exelixis Clinical Site #31
    • New Brunswick New Jersey 08903 United States
    • Exelixis Clinical Site #37
    • Bronx New York 10461 United States
    • Exelixis Clinical Site #40
    • East Setauket New York 11733 United States
    • Exelixis Clinical Site #11
    • New York New York 10029 United States
    • Exelixis Clinical Site #49
    • Columbus Ohio 43210 United States
    • Exelixis Clinical Site #6
    • Oklahoma City Oklahoma 73120 United States
    • Exelixis Clinical Site #45
    • Portland Oregon 97239 United States
    • Exelixis Clinical Site #41
    • Bethlehem Pennsylvania 18015 United States
    • Exelixis Clinical Site #15
    • Philadelphia Pennsylvania 19107 United States
    • Exelixis Clinical Site #55
    • Philadelphia Pennsylvania 19111 United States
    • Exelixis Clinical Site #13
    • Dallas Texas 75246 United States
    • Exelixis Clinical Site #26
    • Dallas Texas 75390 United States
    • Exelixis Clinical Site #29
    • Houston Texas 77030 United States
    • Exelixis Clinical Site #39
    • Houston Texas 77030 United States
    • Exelixis Clinical Site #44
    • Houston Texas 77030 United States
    • Exelixis Clinical Site #33
    • Lubbock Texas 79410 United States
    • Exelixis Clinical Site #2
    • Salt Lake City Utah 84112 United States
    • Exelixis Clinical Site #30
    • Blacksburg Virginia 24060 United States
    • Exelixis Clinical Site #14
    • Charlottesville Virginia 22908 United States
    • Exelixis Clinical Site #52
    • Gent 9000 Belgium
    • Exelixis Clinical Site #54
    • Leuven 3000 Belgium
    • Exelixis Clinical Site #8
    • Villejuif Cedex 94805 France
    • Exelixis Clinical Site #7
    • Paris 75010 France
    • Exelixis Clinical Site #56
    • Düsseldorf Nordrhein-Westfalen 40225 Germany
    • Exelixis Clinical Site #36
    • Tübingen 72076 Germany
    • Exelixis Clinical Site #47
    • Rozzano Milano 20089 Italy
    • Exelixis Clinical Site #25
    • Milano 20133 Italy
    • Exelixis Clinical Site #4
    • Milano 20133 Italy
    • Exelixis Clinical Site #12
    • Nijmegen Gelderland 6525 GA Netherlands
    • Exelixis Clinical Site #28
    • Barcelona 08035 Spain
    • Exelixis Clinical Site #9
    • Barcelona 08035 Spain
    • Exelixis Clinical Site #22
    • Madrid 28041 Spain
    • Exelixis Clinical Site #5
    • Madrid 28041 Spain
    • Exelixis Clinical Site #19
    • London EC1M 6BQ United Kingdom

    View trial on ClinicalTrials.gov


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    Published July 28, 2019
  • A Phase 2, Randomized, Non-Comparative, Open-Label Study of NKTR-214 in Combination With Nivolumab and of Chemotherapy in Cisplatin Ineligible, Locally Advanced or Metastatic Urothelial Cancer Patients With Low PD-L1 Expression

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    A Phase 2, Single-Arm Study of Bempegaldesleukin (NKTR-214) in Combination With Nivolumab in Cisplatin Ineligible, Locally Advanced or Metastatic Urothelial Cancer Patients


    Condition: Urinary Bladder Neoplasm, Neoplasm Metastasis

    Intervention:

    • Biological: Bempegaldesleukin
    • Biological: Nivolumab

    Purpose: The main purpose of this study is to evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03785925

    Sponsor: Nektar Therapeutics

    Primary Outcome Measures:

    • Measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Blinded Independent Central Review (BICR) in patients whose tumors have low programmed cell death ligand (PD-L1) expression
    • Time Frame: Approximately 6 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: ORR by RECIST 1.1 per BICR in all treated patients
    • Time Frame: Approximately 6 months
    • Safety Issue:
    • Measure: Duration of Response (DOR) by RECIST 1.1 per BICR in all treated patients and patients whose tumors have low PD-L1 expression
    • Time Frame: Approximately 2 years
    • Safety Issue:
    • Measure: ORR and DOR by RECIST 1.1 per Investigator assessment in all treated patients and in patients whose tumors have low PD-L1 expression
    • Time Frame: Approximately 2 years
    • Safety Issue:
    • Measure: Incidence of treatment-related Adverse Events (AEs)
    • Time Frame: Up to 2 years
    • Safety Issue:

    Estimated Enrollment: 205

    Study Start Date: April 29, 2019

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Provide written, informed consent to participate in the study and follow the study procedures
    • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
    • Measurable disease per RECIST 1.1 criteria
    • Histologically or cytologically documented inoperable, locally advanced or metastatic urothelial cell carcinoma (also termed TCC)
    • Fresh biopsy or archival tissue
    • No prior systemic chemotherapy or investigational agent for inoperable locally advanced or mUC
    • Ineligible for cisplatin Exclusion Criteria:
    • Patients who have an active, known or suspected autoimmune disease
    • Patients must not have received prior IL-2 therapy
    • Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
    • Patients with hypertension must be on a stable antihypertensive regimen for the 14 days prior to Cycle 1 Day 1 Other protocol-defined inclusion/

    Exclusion Criteria:

    • Patients who have an active, known or suspected autoimmune disease
    • Patients must not have received prior IL-2 therapy
    • Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
    • Patients with hypertension must be on a stable antihypertensive regimen for the 14 days prior to Cycle 1 Day 1 Other protocol-defined inclusion/exclusion criteria could apply

    Contact:

    • Nektar Recruitment
    • 855-482-8676

    Locations:

    • Investigator Site - Anchorage
    • Anchorage Alaska 99503 United States
    • Local Institution - Tucson
    • Tucson Arizona 85710 United States
    • Local Institution - Orange
    • Orange California 92868 United States
    • Investigator Site - Whittier
    • Whittier California 90603 United States
    • Local Institution - Aurora
    • Aurora Colorado 80012 United States
    • Local Institution - Pensacola
    • Pensacola Florida 32503 United States
    • Local Institution - Sanford
    • Sanford Florida 32763 United States
    • Local Institution - Atlanta
    • Atlanta Georgia 30322 United States
    • Local Institution - Newnan
    • Newnan Georgia 30265 United States
    • Investigator Site - Peoria
    • Peoria Illinois 61615 United States
    • Investigator Site - Billings
    • Billings Montana 59102 United States
    • Local Institution - Allentown
    • Allentown Pennsylvania 18103 United States
    • Investigator Site - Bethlehem
    • Bethlehem Pennsylvania 18015 United States
    • Local Institution - Philadelphia
    • Philadelphia Pennsylvania 19107 United States
    • Local Institution - Chattanooga
    • Chattanooga Tennessee 37403 United States
    • Local Institution - Houston
    • Houston Texas 77030 United States
    • Local Institution - San Antonio
    • San Antonio Texas 78229 United States
    • Local Institution - Ciudad Autonoma de Buenos Aire
    • Ciudad Autonoma de Buenos Aire Buenos Aires C1125ABD Argentina
    • Local Institution - Pergamino
    • Pergamino Buenos Aires 2700 Argentina
    • Local Institution - Viedma
    • Viedma Rio Negro R8500ACE Argentina
    • Local Institution - Rosario
    • Rosario Santa Fe S2000DSK Argentina
    • Local Institution - San Miguel De Tucumán
    • San Miguel De Tucumán Tucumán 4000 Argentina
    • Local Institution - Buenos Aires
    • Buenos Aires C1118AAT Argentina
    • Local Institution - Buenos Aires
    • Buenos Aires C1426ANZ Argentina
    • Local Institution - Córdoba
    • Córdoba X5000HHW Argentina
    • Local Institution - Córdoba
    • Córdoba X5002AOQ Argentina
    • Local Institution - Darlinghurst
    • Darlinghurst New South Wales 2010 Australia
    • Investigator Site - Auchenflower
    • Auchenflower Queensland 4066 Australia
    • Local Institution - Southport
    • Southport Queensland 4215 Australia
    • Investigator Site - Kurralta Park
    • Kurralta Park South Australia 5037 Australia
    • Local Institution - Bentleigh East
    • Bentleigh East Victoria 3165 Australia
    • Investigator Site - Nedlands
    • Nedlands Western Australia 6009 Australia
    • Investigator Site - Wien
    • Wien 1020 Austria
    • Local Institution - Brasschaat
    • Brasschaat Antwerpen 2930 Belgium
    • Local Institution - Wilrijk
    • Wilrijk Antwerpen 2610 Belgium
    • Local Institution - Kortrijk
    • Kortrijk Belgium
    • Local Institution - Salvador
    • Salvador Bahia 41820-021 Brazil
    • Local Institution - Ijuí
    • Ijuí Rio Grande Do Sul 98700-000 Brazil
    • Local Institution - Lajeado
    • Lajeado Rio Grande Do Sul 95900-000 Brazil
    • Local Institution - Porto Alegre
    • Porto Alegre Rio Grande Do Sul 90035-903 Brazil
    • Local Institution - Porto Alegre
    • Porto Alegre Rio Grande Do Sul 90110-270 Brazil
    • Local Institution - Porto Alegre
    • Porto Alegre Rio Grande Do Sul 91350-200 Brazil
    • Local Institution - São Paulo
    • Barretos São Paulo 14784-400 Brazil
    • Local Institution - Jaú
    • Jaú São Paulo 17210-120 Brazil
    • Local Institution - Lages
    • Lages 88501-001 Brazil
    • Local Institution - São José Do Rio Preto
    • São José Do Rio Preto 15090-000 Brazil
    • Local Institution - Copenhagen
    • Copenhagen 2100 Denmark
    • Local Institution - Næstved
    • Næstved 4700 Denmark
    • Local Institution - Helsinki
    • Helsinki 00290 Finland
    • Local Institution - Caen
    • Caen Calvados 14076 France
    • Local Institution - Hyères
    • Hyères 83400 France
    • Local Institution - Le Mans
    • Le Mans 72015 France
    • Local Institution - Paris
    • Paris 75908 France
    • Local Institution - Saint-Herblain
    • Saint-Herblain 44805 France
    • Local Institution - Strasbourg
    • Strasbourg 67000 France
    • Local Institution - Villejuif
    • Villejuif 94805 France
    • Local Institution - Nürtingen
    • Nürtingen Baden-Württemberg 72622 Germany
    • Local Institution - Weiden
    • Weiden Bavaria 92637 Germany
    • Local Institution - Münster
    • Münster Nordrhein-Westfalen 48149 Germany
    • Local Institution - Berlin
    • Berlin 10117 Germany
    • Local Institution - Dresden
    • Dresden 01307 Germany
    • Local Institution - Athens
    • Athens Attiki 115 28 Greece
    • Local Institution - Athens
    • Athens Attiki 145 64 Greece
    • Local Institution - Larissa
    • Larissa 41110 Greece
    • Local Institution - Thessaloníki
    • Thessaloníki 54622 Greece
    • Investigator Site - Thessaloníki
    • Thessaloníki 54645 Greece
    • Local Institution - Zerifin
    • Zerifin HaMerkaz 70300 Israel
    • Local Institution - Haifa
    • Haifa 31096 Israel
    • Local Institution - Kfar Saba
    • Kfar Saba 44281 Israel
    • Investigator Site - Petah tikva
    • Petah tikva 49100 Israel
    • Local Institution - Ramat Gan
    • Ramat Gan 52621 Israel
    • Local Institution - Tel Aviv
    • Tel Aviv 52620 Israel
    • Local Institution - Meldola
    • Meldola Emilia-Romagna 47014 Italy
    • Local Institution - Milano
    • Milano 20162 Italy
    • Local Institution - Napoli
    • Napoli 80131 Italy
    • Local Institution - Morelia
    • Morelia Michoacán 58260 Mexico
    • Local Institution - Cuautitlán Izcalli
    • Cuautitlán Izcalli 54769 Mexico
    • Local Institution - Monterrey
    • Monterrey 64000 Mexico
    • Local Institution - Amsterdam
    • Amsterdam 1066 Netherlands
    • Local Institution - Groningen
    • Groningen 9713 GZ Netherlands
    • Local Institution - Toruń
    • Toruń Kujawsko-Pomorskie 87-100 Poland
    • Local Institution - Coimbra
    • Coimbra 3000-075 Portugal
    • Local Institution - San Juan
    • San Juan 00921 Puerto Rico
    • Local Institution - Yaroslavl
    • Yaroslavl Yaroslavskaya Oblast 150040 Russian Federation
    • Local Institution - Obninsk
    • Obninsk 249036 Russian Federation
    • Local Institution - Omsk
    • Omsk 644013 Russian Federation
    • Investigator Site - Pushkin
    • Pushkin 196603 Russian Federation
    • Local Institution - Saint Petersburg
    • Saint Petersburg 195271 Russian Federation
    • Local Institution - Volzhskiy
    • Volzhskiy 404120 Russian Federation
    • Local Institution - Elche
    • Elche Alicante 03203 Spain
    • Local Institution - Barcelona
    • Barcelona Catalonia 08025 Spain
    • Local Institution - Madrid
    • Pozuelo De Alarcón Madrid 28223 Spain
    • Investigator Site - Pamplona
    • Pamplona Navarra 31008 Spain
    • Local Institution - Madrid
    • Madrid 28007 Spain
    • Local Institution - Madrid
    • Madrid 28034 Spain
    • Local Institution - Madrid
    • Madrid 28041 Spain
    • Local Institution - Madrid
    • Madrid 28050 Spain
    • Local Institution - Sevilla
    • Sevilla 41013 Spain
    • Local Institution - Valencia
    • Valencia 46009 Spain
    • Local Institution - Ankara
    • Ankara 6100 Turkey
    • Local Institution - Istanbul
    • Istanbul 34098 Turkey
    • Local Institution - Istanbul
    • Istanbul 34732 Turkey
    • Local Institution - İzmir
    • İzmir 35530 Turkey
    • Local Institution - Malatya
    • Malatya 44280 Turkey
    • Local Institution - Leicester
    • Leicester LE1 5WW United Kingdom
    • Local Institution - London
    • London SW6 7JT United Kingdom

    View trial on ClinicalTrials.gov


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    Published August 9, 2019
  • A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGF

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    A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGFR Genomic Alterations


    Condition: Urothelial Cancer

    Intervention:

    • Drug: JNJ-42756493

    Purpose: The purpose of this study is to evaluate the objective response rate (complete response [CR]+ partial response [PR]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02365597

    Sponsor: Janssen Research & Development, LLC

    Primary Outcome Measures:

    • Measure: Percentage of Participants with Best Overall Response
    • Time Frame: 1 year
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Progression-free survival
    • Time Frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (approximately 3 years 9 months)
    • Safety Issue:
    • Measure: Duration of Response
    • Time Frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (approximately 3 years 9 months)
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: From the date of the first dose of study drug until death (up to 3 years 9 months)
    • Safety Issue:
    • Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
    • Time Frame: Screening up to end of study (approximately 3 years 9 months)
    • Safety Issue:
    • Measure: Percentage of Participants With Biomarker Assessment
    • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
    • Safety Issue:
    • Measure: Plasma Concentration of JNJ 42756493
    • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
    • Safety Issue:
    • Measure: Plasma Clearance of JNJ 42756493
    • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
    • Safety Issue:
    • Measure: Volume of Distribution of JNJ 42756493
    • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
    • Safety Issue:

    Estimated Enrollment: 210

    Study Start Date: April 22, 2015

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
    • Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
    • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2
    • Must have adequate bone marrow, liver, and renal function as described in protocol
    • Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active
    • Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These subjects will be referred to as chemo-refractory subjects. (Subjects who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible)

    Exclusion Criteria:

    • Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted
    • Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management
    • Has a history of or current uncontrolled cardiovascular disease
    • Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug
    • Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

    Contact:

    • Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:

    Locations:

    • Mayo Clinic Arizona
    • Scottsdale Arizona 85259 United States
    • Arizona Oncology Associates, PC - NAHOA
    • Sedona Arizona 86336 United States
    • University of Arizona Cancer Center
    • Tucson Arizona 85724 United States
    • Marin Cancer Care Inc.
    • Greenbrae California 94904 United States
    • Cedars Sinai Medical Center - Pediatric Infectious Disease
    • Los Angeles California 90048 United States
    • Ronald Reagan UCLA Medical Center
    • Los Angeles California 90095 United States
    • University of California - Davis Medical Center
    • Sacramento California 95817 United States
    • Stanford University Medical Center
    • Stanford California 94305 United States
    • Rocky Mountain Cancer Center
    • Aurora Colorado 80012 United States
    • Georgetown Univ. Medical Center - Lombardi Cancer Center
    • Washington District of Columbia 20007 United States
    • Northwestern University Feinberg School of Medicine
    • Chicago Illinois 60611 United States
    • University of Chicago
    • Chicago Illinois 60637 United States
    • The University of Iowa - Division of Hematology, Oncology and Blood & Marrow Transplantation
    • Iowa City Iowa 52242 United States
    • Norton Cancer Institute
    • Louisville Kentucky 40202 United States
    • Univ of Michigan Medical Center
    • Ann Arbor Michigan 48109 United States
    • Karmanos Cancer Institute - Wayne State University
    • Detroit Michigan 48201 United States
    • Minnesota Oncology
    • Minneapolis Minnesota 55404 United States
    • Nebraska Cancer Specialists
    • Omaha Nebraska 68130 United States
    • Comprehensive Cancer Centers of Nevada
    • Las Vegas Nevada 89169 United States
    • Rutgers Cancer Institute of New Jersey
    • New Brunswick New Jersey 08903 United States
    • Weill Medical College of Cornell University
    • New York New York 10021 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10065 United States
    • Levine Cancer Institute
    • Charlotte North Carolina 28204 United States
    • Hematology Oncology Associates, PC
    • Medford Oregon 97504 United States
    • Northwest Cancer Specialists PC
    • Tualatin Oregon 97062 United States
    • Penn State Milton S. Hershey Medical Ctr.
    • Hershey Pennsylvania 17033 United States
    • University of Pittsburgh Medical Center (UPMC)
    • Pittsburgh Pennsylvania 15232 United States
    • Carolina Urologic Research Center
    • Myrtle Beach South Carolina 29572 United States
    • SCRI - Sarah Cannon Research Institute
    • Nashville Tennessee 37203 United States
    • Texas Oncology-Dallas Presbyterian Hospital
    • Dallas Texas 75231 United States
    • Texas Oncology - Sammons Cancer Center
    • Dallas Texas 75246 United States
    • UT Southwestern Medical Center
    • Dallas Texas 75390 United States
    • Texas Oncology-Denton South
    • Denton Texas 76210 United States
    • Texas Oncology-Memorial City
    • Houston Texas 77024 United States
    • University of Texas MD Anderson Cancer Center
    • Houston Texas 77030 United States
    • Virginia Oncology Associates
    • Hampton Virginia 23666 United States
    • University of Wisconsin School of Medicine and Public Health
    • Madison Wisconsin 53792 United States
    • LKH-Univ. Klinikum Graz
    • Graz A-8036 Austria
    • Krankenhaus der Barmherzigen Schwestern Linz
    • Linz 4020 Austria
    • Krankenhaus der Barmherzigen Brüder
    • Vienna 1020 Austria
    • Medical University Vienna
    • Vienna A-1090 Austria
    • O.L.V. Ziekenhuis
    • Aalst 9300 Belgium
    • Cliniques Universitaires Saint Luc
    • Brussel 1200 Belgium
    • Clinique Notre Dame
    • Charleroi 6000 Belgium
    • U.Z. Gent
    • Gent 9000 Belgium
    • GZA Ziekenhuizen- Campus St Augustinus
    • Wilrijk 2610 Belgium
    • ICO, Site Paul Papin
    • Angers Cedex 49055 France
    • Institut Bergonié
    • Bordeaux France
    • Centre Francois Baclesse
    • Caen Cédex 05 14076 France
    • Centre Georges-François Leclerc
    • Dijon 21000 France
    • Centre Leon Bérard
    • Lyon 69008 France
    • Centre Antoine Lacassagne
    • Nice Cedex 2 06189 France
    • Institut de Cancérologie du Gard
    • Nîmes 30029 France
    • Hospital Saint-Louis
    • Paris Cedex 10 75475 France
    • Hopital Europeen Georges-Pompidou
    • Paris Cedex 15 75908 France
    • I.C.O. René Gauducheau
    • Saint Herblain Cedex 44805 France
    • Hopital Foch
    • Suresnes 92150 France
    • Institut Universitaire du Cancer Toulouse - Oncopole
    • Toulouse Cedex 09 31059 France
    • Gustave Roussy
    • Villejuif Cedex 94805 France
    • Vivantes Klinikum Am Urban, Abt. fur Kardiologie
    • Berlin 10967 Germany
    • Waldkrankenhaus St. Marien -Urologische Universitätsklinik-
    • Erlangen 91054 Germany
    • Kliniken Essen-Mitte; Evangelische Huyssens-Stiftung
    • Essen 45136 Germany
    • Goethe Universität Frankfurt
    • Frankfurt 60590 Germany
    • Universitatsklinikum Freiburg
    • Freiburg 79106 Germany
    • Universitätsmedizin Greifswald
    • Greifswald 17475 Germany
    • Georg-August-Universitaet Goettingen - Innere Medizin - Haematologie, Onkologie
    • Göttingen 37075 Germany
    • Asklepios Klinik Altona
    • Hamburg 22763 Germany
    • Medizinische Hochschule Hannover;Klinik f. Urologie u. Urologische Onkologie
    • Hannover 30625 Germany
    • University Hospital Heidelberg
    • Heidelberg 69120 Germany
    • Klinikum rechts der Isar der TU Muenchen
    • Muenchen 81675 Germany
    • University hospital Muenster, Dpt. of Urology
    • Muenster 48129 Germany
    • Caritas Krankenhaus St. Josef - Innere Medizin II
    • Regensburg 93053 Germany
    • Klinikum St. Elisabeth
    • Straubing 94315 Germany
    • Kliniken Nordoberpfalz, Klinik für Urologie
    • Weiden/Opf 92637 Germany
    • Soroka Medical Center
    • Beer Sheba 84101 Israel
    • Asaf Harofe Medical Center
    • Beer Yaakov 60930 Israel
    • Rambam Medical Center
    • Haifa 31096 Israel
    • Meir Medical Center
    • Kfar-Saba 44281 Israel
    • Rabin Medical Center - Bellins
    • Petah Tikva 49100 Israel
    • Sourasky Medical Center, Tel Aviv Sourasky Med Ctr
    • Tel-Aviv 64239 Israel
    • Unità Operativa di Oncologia Medica
    • Arezzo 52100 Italy
    • Oncologia-IRCCS IRST
    • Meldola 47014 Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano 20100 Italy
    • Oncologia Medica A - Ist Naz Tumori G Pascale
    • Napoli 80131 Italy
    • Ospedale Maggiore della Carità
    • Novara 28100 Italy
    • Oncologia Medica Azienda Sanitaria Ospedaliera San Luigi Gonzaga
    • Orbassano 10043 Italy
    • Istituto Oncologico Veneto - IRCCS
    • Padova 35128 Italy
    • Oncologia Medica - Azienda Ospedaliero Universitaria Di Parma
    • Parma 43126 Italy
    • Azienda Ospedaliero Universitaria Pisana
    • Pisa 56126 Italy
    • Azienda Ospedaliera San Camillo - Roma
    • Roma 00152 Italy
    • UOC di Oncologia Medica Università Cattolica del Sacro Cuore Policlinico Universitario A. Gemelli
    • Roma 00168 Italy
    • University Hospital Umberto I
    • Rome 00161 Italy
    • Istituto Clinico Humanitas UO di Emodinamica e Cradiologia Interventistica
    • Rozzano 20089 Italy
    • Oncologia Medica-Città Della Salute E Della Scienza Di Torino
    • Torino 10126 Italy
    • Azienda Ospedaliero - Universitaria Ospedali Riuniti
    • Torrette Di Ancona 60126 Italy
    • Chungnam National University Hospital - Dept. of Internal Medicine
    • Daejeon 301-721 Korea, Republic of
    • National Cancer Center
    • Goyangsi 410-769 Korea, Republic of
    • Gachon University Gil Medical Center
    • Incheon 21565 Korea, Republic of
    • Severance Hospital
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center (AMC)
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 135-710 Korea, Republic of
    • Arensia Exploratory Medicine
    • Chisinau MD 2025 Moldova, Republic of
    • Spitalul Clinic de Urologie Prof. Dr. Theodor Burghele
    • Bucharest 050659 Romania
    • Spitalul Clinic Sf. Maria
    • Bucharest 11172 Romania
    • Institutul Clinic Fundeni
    • Bucuresti 022328 Romania
    • Arensia Exploratory Medicine - Romania
    • Bucuresti 050159 Romania
    • Institutul Oncologic "Prof Dr. Ion Chiricuta" Cluj-Napoca
    • Cluj-Napoca 400015 Romania
    • ONCOLAB
    • Craiova 200385 Romania
    • Institutul Regional de Oncologie Iasi
    • Iasi 700483 Romania
    • Spitalul Clinic Municipal De Urgenta Timisoara; Sectia Oncologie
    • Timisoara Romania
    • Altai Regional Oncology Dispensary
    • Barnaul 656049 Russian Federation
    • Cancer Research Center
    • Moscow N/A 115478 Russian Federation
    • Scientific Research Institute of Urology
    • Moscow 105425 Russian Federation
    • Hertzen Oncology Research Institute
    • Moscow 125284 Russian Federation
    • Clinical Oncology Dispensary
    • Omsk 644013 Russian Federation
    • Pyatigorsk Regional Oncology Dispensary
    • Pyatigorsk 357502 Russian Federation
    • Leningradski Regional Oncological Dispensary
    • Saint-Petersburg 191104 Russian Federation
    • Russian Scientific Center of Radiology and Surgical Technologies
    • Saint-Petersburg 197758 Russian Federation
    • Bashkiria State Medical University
    • Ufa 450000 Russian Federation
    • Hospital Universitari Germans Trias i Pujol
    • Badalona Spain
    • Hospital Universitario Vall d´Hebron
    • Barcelona 08035 Spain
    • Hospital Clinic de Barcelona
    • Barcelona 08036 Spain
    • Hospital U. Gregorio Marañón
    • Madrid 28007 Spain
    • Fundacion Jimenez Diaz
    • Madrid 28020 Spain
    • Hospital Universitario La Paz
    • Madrid 28046 Spain
    • Centro Integral Oncológico Clara Campal
    • Madrid 28050 Spain
    • Hosp. Virgen de La Victoria
    • Málaga 29010 Spain
    • Clinica Universitaria de Navarra
    • Pamplona 31008 Spain
    • Hospital Virgen del Rocío
    • Sevilla 41013 Spain
    • Taichung Veterans General Hospital
    • Taichung 40705 Taiwan
    • National Cheng Kung University Hospital
    • Tainan 70403 Taiwan
    • National Taiwan University Hospital
    • Taipei 10002 Taiwan
    • Chang Gung Memorial Hospital- Linkou
    • Taoyuan 333 Taiwan
    • Royal Blackburn Hospital
    • Blackburn BB2 3HH United Kingdom
    • Ninewells Hospital
    • Dundee DD1 9SY United Kingdom
    • Queens Hospital
    • Essex RM7 0AG United Kingdom
    • Charing Cross Hospital
    • London W6 8RF United Kingdom
    • Derriford Hospital
    • Plymouth PL6 8DH United Kingdom
    • Royal Marsden Hospital
    • Sutton SM2 5PT United Kingdom
    • Clatterbridge Centre for Oncology
    • Wirral CH63 4JY United Kingdom

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemothera

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    A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)


    Condition: UC (Urothelial Cancer)

    Intervention:

    • Drug: Pembrolizumab
    • Drug: Epacadostat
    • Drug: Placebo

    Purpose: The purpose of this study is to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic urothelial carcinoma in patients who have failed a first-line platinum-containing chemotherapy regimen for advanced/metastatic disease.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03374488

    Sponsor: Incyte Corporation

    Primary Outcome Measures:

    • Measure: Overall survival (OS) with pembrolizumab + epacadostat versus pembrolizumab + placebo
    • Time Frame: Up to 27 months
    • Safety Issue:
    • Measure: Progression-free survival (PFS) with pembrolizumab + epacadostat versus pembrolizumab + placebo
    • Time Frame: Up to 27 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo
    • Time Frame: Approximately 24 months
    • Safety Issue:
    • Measure: Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
    • Time Frame: Up to 27 months
    • Safety Issue:
    • Measure: Number of participants discontinuing study treatment due to AEs compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
    • Time Frame: Up to 27 months
    • Safety Issue:
    • Measure: Mean change from baseline in global health status/quality of life scales
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Time to true deterioration (TTD)
    • Time Frame: Up to 25 months
    • Safety Issue:

    Estimated Enrollment: 648

    Study Start Date: December 22, 2017

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
    • Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ≤ 12 months following completion of therapy.
    • Measurable disease based on RECIST v1.1.
    • Have provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for PD-L1 analysis.
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    • Adequate organ function per protocol-defined criteria.

    Exclusion Criteria:

    • Urothelial carcinoma that is suitable for local therapy with curative intent.
    • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
    • Known additional malignancy that is progressing or has required active treatment within the past 3 years.
    • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging.
    • Active autoimmune disease that has required systemic treatment in past 2 years.
    • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
    • Known history of or is positive for active hepatitis B (HBsAg reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
    • Use of protocol-defined prior/concomitant therapy.

    Contact:

    • Incyte Corporation Call Center (US)
    • 1.855.463.3463

    Locations:

    • Ironwood Cancer & Research Centers
    • Chandler Arizona 85224 United States
    • University of California Irvine Medical Center
    • Orange California 92868 United States
    • University of California San Francisco
    • San Francisco California 94107 United States
    • UCLA Hematology Oncology Santa Monica
    • Santa Monica California 90404 United States
    • Smilow Cancer Center at Yale-New Haven
    • New Haven Connecticut 06510 United States
    • Northside Hospital, Inc. - GCS/Annex
    • Atlanta Georgia 30341 United States
    • University of Chicago
    • Chicago Illinois 60637 United States
    • Quincy Medical Group
    • Quincy Illinois 62301 United States
    • Johns Hopkins University
    • Baltimore Maryland 21287 United States
    • Massachusetts General Hospital
    • Boston Massachusetts 02114 United States
    • University of Michigan Health System
    • Ann Arbor Michigan 48109 United States
    • NYU Clinical Cancer Center
    • New York New York 10016 United States
    • Oklahoma Cancer Specialists & Research Institute
    • Tulsa Oklahoma 74146 United States
    • Oregon Health & Science University
    • Portland Oregon 97210 United States
    • University of Pennsylvania
    • Philadelphia Pennsylvania 19104 United States
    • Thomas Jefferson University Hospital
    • Philadelphia Pennsylvania 19107 United States
    • Fox Chase Cancer Center
    • Philadelphia Pennsylvania 19111 United States
    • Medical University of South Carolina-Hollings Cancer Center
    • Charleston South Carolina 29425 United States
    • University of Tennessee Medical Center Knoxville
    • Knoxville Tennessee 37920 United States
    • Vanderbilt-Ingram Cancer Center
    • Nashville Tennessee 37232 United States
    • US Oncology and Research
    • Fort Worth Texas 76177 United States
    • VCU Massey Cancer Center
    • Richmond Virginia 23298 United States
    • Southern Medical Day Care Centre
    • Wollongong New South Wales 2500 Australia
    • Austin Health-Austin Hospital
    • Heidelberg Victoria 3084 Australia
    • Adelaide Cancer Centre
    • Kurralta Park 5037 Australia
    • Macquarie University Hospital
    • Macquarie Park 2109 Australia
    • London Health Sciences Centre
    • London Ontario N6A 4L6 Canada
    • The Ottawa Hospital Cancer Centre
    • Ottawa Ontario K1H 8L6 Canada
    • Sunnybrook Research Institute
    • Toronto Ontario M4N 3M5 Canada
    • CIUSSS - Hopital Maisonneuve- Rosemont
    • Montréal Quebec H1T 2M4 Canada
    • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
    • Québec Quebec G1R 3S1 Canada
    • Aalborg University Hospital
    • Aalborg 9000 Denmark
    • Aarhus Universitetshospital
    • Aarhus 8000 Denmark
    • Rigshospitalet
    • Copenhagen 2100 Denmark
    • Herlev Hospital
    • Herlev 2730 Denmark
    • Institut de Cancerologie de l Ouest Site Paul Papin
    • Angers 49055 France
    • Clinique Sainte Catherine
    • Avignon 84918 France
    • Centre de Lutte Contre le Cancer Francois Baclesse
    • Caen 14000 France
    • Clinique Victor Hugo
    • Le Mans 72000 France
    • Centre Oscar Lambret
    • Lille 59020 France
    • Centre Leon Berard
    • Lyon 69008 France
    • Institut du Cancer de Montpellier
    • Montpellier 34298 France
    • Hopital Cochin
    • Paris 75014 France
    • Hopital Saint Louis
    • Paris 75475 France
    • Institut Jean Godinot
    • Reims 51726 France
    • Centre Medico-Chirurgical Foch
    • Suresnes 92151 France
    • C.H.U. de Tours - Hopital Bretonneau
    • Tours 37044 France
    • Institut Gustave Roussy
    • Villejuif 94805 France
    • Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
    • Luebeck Schleswig Holstein 23538 Germany
    • Universitaetsklinikum Duesseldorf
    • Duesseldorf 40225 Germany
    • Universitatsklinikum Hamburg-Eppendorf
    • Hamburg 20246 Germany
    • Universitaetsklinikum Jena
    • Jena 07747 Germany
    • Universitaetsklinikum Magdeburg A.o.R.
    • Magdeburg 39120 Germany
    • Klinikum rechts der Isar der Technischen Universitat
    • Muenchen 81675 Germany
    • Universitaetsklinikum Tuebingen
    • Tuebingen 72076 Germany
    • Orszagos Onkologiai Intezet
    • Budapest 1122 Hungary
    • Uzsoki Utcai Korhaz
    • Budapest 1145 Hungary
    • Somogy Megyei Kaposi Mor Oktato Korhaz
    • Kaposvár 7400 Hungary
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
    • Miskolc 3526 Hungary
    • Pecsi Tudomanyegyetem AOK
    • Pécs 7624 Hungary
    • Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet
    • Szolnok 5004 Hungary
    • Cork University Hospital
    • Cork Ireland
    • Beaumont Hospital
    • Dublin 00009 Ireland
    • Adelaide & Meath Hospital (Incl NCH)
    • Dublin 00024 Ireland
    • University College Hospital Galway
    • Galway H91YR71 Ireland
    • University Hospital Limerick
    • Limerick Ireland
    • Waterford Regional Hospital
    • Waterford X91ER8E Ireland
    • Soroka Medical Center
    • Be'er Sheva 8410101 Israel
    • Rambam Medical Center
    • Haifa 31096 Israel
    • Meir Medical Center
    • Kfar Saba 4428164 Israel
    • Rabin Medical Center
    • Petach-Tikwa 49100 Israel
    • Chaim Sheba Medical Center
    • Ramat Gan 52621 Israel
    • Sourasky Medical Center
    • Tel Aviv 6423906 Israel
    • Assaf Harofeh Medical Center
    • Zerifin 70300 Israel
    • Medical Oncology Ospedale San Donato
    • Arezzo 52100 Italy
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
    • Meldola 47014 Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano 20133 Italy
    • Istituto Nazionale Tumori Fondazione Pascale
    • Napoli 80131 Italy
    • Istituto Oncologico Veneto
    • Padova 35128 Italy
    • Nagoya University Hospital
    • Nagoya Aichi 466-8560 Japan
    • Nara Medical University Hospital
    • Kashihara Nara 634-8522 Japan
    • Yamaguchi University Hospital
    • Ube Yamaguchi 755-8505 Japan
    • Medical Hospital, Tokyo Medical And Dental University
    • Tokyo 113-8519 Japan
    • Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)
    • Tokyo 144-0042 Japan
    • Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)
    • Tokyo 144-0042 Japan
    • Seoul National University Hospital
    • Seoul 03080 Korea, Republic of
    • Severance Hospital Yonsei University Health System
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 06351 Korea, Republic of
    • Antoni van Leeuwenhoek Ziekenhuis
    • Amsterdam 1066 CX Netherlands
    • VU University Medical Center
    • Amsterdam 1081 HV Netherlands
    • Amphia Ziekenhuis
    • Breda 4819 EV Netherlands
    • Catharina Ziekenhuis
    • Eindhoven 5623 EJ Netherlands
    • University Medical Center Groningen
    • Groningen 9713 GZ Netherlands
    • Leningrad Regional Oncology Dispensary
    • Saint Petersburg Leningrad Region, Vsevolozhsky District 188663 Russian Federation
    • Ivanovo Regional Oncology Dispensary
    • Ivanovo 153013 Russian Federation
    • N.N. Blokhin NMRCO
    • Moscow 115478 Russian Federation
    • Russian Scientific Center of Roentgenoradiology
    • Moscow 117997 Russian Federation
    • National Medical Research Radiological Centre
    • Moscow 125284 Russian Federation
    • Ryazan Regional Clinical Oncology Dispensary
    • Ryazan' 390046 Russian Federation
    • Pokrovskaya City Hospital
    • Saint Petersburg 199106 Russian Federation
    • Clinic of Bashkortostan State Medical University
    • Ufa 450000 Russian Federation
    • Hospital del Mar
    • Barcelona 08003 Spain
    • Hospital Vall D Hebron
    • Barcelona 08035 Spain
    • Hospital de la Santa Creu i Sant Pau
    • Barcelona 08041 Spain
    • Hospital General Universitario Gregorio Maranon
    • Madrid 28007 Spain
    • MD Anderson Cancer Center Madrid
    • Madrid 28033 Spain
    • Hospital Universitario Virgen de la Victoria
    • Málaga 29010 Spain
    • Hospital Clinico Universitario de Santiago
    • Santiago De Compostela 15706 Spain
    • Instituto Valenciano de Oncologia
    • Valencia 46009 Spain
    • Chang Gung Medical Foundation. Kaohsiung Branch
    • Kaohsiung 833 Taiwan
    • China Medical University Hospital
    • Taichung 40447 Taiwan
    • National Cheng Kung University Hospital
    • Tainan 704 Taiwan
    • National Taiwan University Hospital
    • Taipei 100 Taiwan
    • Taipei Veterans General Hospital
    • Taipei 11217 Taiwan
    • Adana Numune Egitim ve Arastirma Hastanesi
    • Adana 01358 Turkey
    • Adana Sehir Hastanesi
    • Adana 01370 Turkey
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH
    • Ankara 06200 Turkey
    • Akdeniz Universitesi Tip Fakultesi
    • Antalya 07059 Turkey
    • Pamukkale Unv. Tip Fak.
    • Denizli 20070 Turkey
    • Trakya Universitesi Tip Fakultesi
    • Edirne 22030 Turkey
    • Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi
    • Istanbul 34899 Turkey
    • Dokuz Eylul University Faculty of Medicine
    • İzmir 35340 Turkey
    • Samsun Medical Park Hastanesi
    • Samsun 55200 Turkey
    • Royal Marsden NHS Trust
    • Sutton Surrey SM2 5PT United Kingdom
    • Queen Elizabeth Hospital
    • Birmingham B15 2TH United Kingdom
    • Barts Health NHS Trust - St Bartholomew s Hospital
    • London EC1A 7BE United Kingdom
    • Royal Free London NHS Foundation Trust
    • London NW3 2QG United Kingdom
    • Imperial College Healthcare NHS Trust
    • London W6 8RF United Kingdom
    • Plymouth Hospitals NHS Trust
    • Plymouth PL6 8DH United Kingdom
    • Sunderland Royal Hospital
    • Sunderland SR4 7TP United Kingdom

    View trial on ClinicalTrials.gov


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    Published January 25, 2018
  • A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

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    A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)


    Condition: UC (Urothelial Cancer)

    Intervention:

    • Drug: Pembrolizumab
    • Drug: Epacadostat
    • Drug: Placebo

    Purpose: The purpose of this study is to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03361865

    Sponsor: Incyte Corporation

    Primary Outcome Measures:

    • Measure: Progression-free survival (PFS) with pembrolizumab + epacadostat versus pembrolizumab + placebo
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Overall survival (OS) with pembrolizumab + epacadostat versus pembrolizumab + placebo
    • Time Frame: Up to 36 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
    • Time Frame: Up to 39 months
    • Safety Issue:
    • Measure: Number of participants discontinuing study treatment due to AEs compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
    • Time Frame: Up to 39 months
    • Safety Issue:
    • Measure: Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo
    • Time Frame: Approximately 24 months
    • Safety Issue:
    • Measure: Mean change from baseline in global health status/quality of life scales
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Time to true deterioration (TTD)
    • Time Frame: Up to 25 months
    • Safety Issue:

    Estimated Enrollment: 650

    Study Start Date: December 22, 2017

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.
    • Measurable disease based on RECIST v1.1.
    • Be considered ineligible to receive cisplatin-based combination therapy, based on protocol-defined criteria.
    • Have provided tissue for PD-L1 analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
    • Have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to randomization.
    • Adequate organ function per protocol-defined criteria.

    Exclusion Criteria:

    • Disease that is suitable for local therapy administered with curative intent.
    • Known additional malignancy that is progressing or has required active treatment within the past 3 years.
    • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
    • Active autoimmune disease that has required systemic treatment in past 2 years.
    • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
    • Known history of or is positive for active hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
    • History of a gastrointestinal condition that in the opinion of the Investigator may affect oral drug absorption.
    • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
    • Use of protocol-defined prior/concomitant therapy.

    Contact:

    • Incyte Corporation Call Center (US)
    • 1.855.463.3463

    Locations:

    • Arizona Oncology Associates PC- HOPE
    • Tucson Arizona 85704 United States
    • University of California Irvine Medical Center
    • Orange California 92868 United States
    • Yale Cancer Center
    • New Haven Connecticut 06511 United States
    • Woodlands Medical Specialists, PA
    • Pensacola Florida 32503 United States
    • Rush University Medical Center
    • Chicago Illinois 60612 United States
    • Massachusetts General Hospital
    • Boston Massachusetts 02114 United States
    • Comprehensive Cancer Centers of Nevada
    • Las Vegas Nevada 89169 United States
    • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • New York New York 10016 United States
    • Levine Cancer Institute
    • Charlotte North Carolina 28204 United States
    • Willamette Valley Cancer Institute and Research Center
    • Eugene Oregon 97401 United States
    • Abramson Cancer Center of the University of Pennsylvania
    • Philadelphia Pennsylvania 19104 United States
    • Fox Chase Cancer Center
    • Philadelphia Pennsylvania 19111 United States
    • Medical University of South Carolina-Hollings Cancer Center
    • Charleston South Carolina 29425 United States
    • Tennessee Oncology-Chattanooga
    • Chattanooga Tennessee 37404 United States
    • University of Tennessee Medical Center Knoxville
    • Knoxville Tennessee 37920 United States
    • Tennessee Oncology Nashville
    • Nashville Tennessee 37203 United States
    • Vanderbilt-Ingram Cancer Center
    • Nashville Tennessee 37232 United States
    • Texas Oncology PA
    • Houston Texas 77024 United States
    • Calvary Mater Newcastle
    • Waratah New South Wales 2298 Australia
    • Southern Medical Day Care Centre
    • Wollongong New South Wales 2500 Australia
    • Austin Health-Austin Hospital
    • Heidelberg Victoria 3084 Australia
    • Adelaide Cancer Centre
    • Kurralta Park 5037 Australia
    • Macquarie University Hospital
    • Macquarie Park 2109 Australia
    • Institut Jules Bordet
    • Bruxelles 1000 Belgium
    • Grand Hopital de Charleroi - Site Notre Dame - Oncology
    • Charleroi 6000 Belgium
    • AZ Maria Middelares Gent
    • Gent 9000 Belgium
    • Universitair Ziekenhuis Gent
    • Gent 9000 Belgium
    • Hopital de Jolimont
    • Haine-Saint-Paul 7100 Belgium
    • AZ Nikolaas
    • Sint-Niklaas 9100 Belgium
    • GZA Sint Augustinus
    • Wilrijk 2610 Belgium
    • Moncton Hospital - Horizon Health Network
    • Moncton New Brunswick E1C 6Z8 Canada
    • Cancer Centre of Southeastern Ontario at Kingston General Hospital
    • Kingston Ontario K7L 2V7 Canada
    • Ottawa General Hospital
    • Ottawa Ontario K1H 8L6 Canada
    • Sunnybrook Health Science Centre
    • Toronto Ontario M4N 3M5 Canada
    • CIUSSS - Hopital Maisonneuve-Rosemont
    • Montreal Quebec H1T 2M4 Canada
    • CHU de Quebec - Hotel-Dieu de Quebec
    • Québec Quebec G1R 2J6 Canada
    • Institut de Cancerologie de l Ouest Site Paul Papin
    • Angers 49055 France
    • CHU de Besancon
    • Besançon 25030 France
    • Institut Bergonie
    • Bordeaux 33076 France
    • Centre Jean Perrin
    • Clermont-Ferrand 63011 France
    • Institut Paoli Calmettes
    • Marseille 13009 France
    • Centre d Oncologie de Gentilly
    • Nancy 54100 France
    • Hopital Europeen Georges Pompidou
    • Paris 75908 France
    • Centre Hospitalier Lyon Sud
    • Pierre-Bénite 69310 France
    • Institut Jean Godinot
    • Reims 51726 France
    • CHU de Strasbourg - Nouvel Hopital Civil
    • Strasbourg 67091 France
    • Institut Claudius Regaud
    • Toulouse 31059 France
    • C.H.U. de Tours - Hopital Bretonneau
    • Tours 37044 France
    • Institut Gustave Roussy
    • Villejuif 94805 France
    • Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
    • Luebeck Schleswig Holstein 23538 Germany
    • Universitaetsklinikum Duesseldorf
    • Duesseldorf 40225 Germany
    • Kliniken Essen Mitte
    • Essen 45136 Germany
    • Universitatsklinikum Hamburg-Eppendorf
    • Hamburg 20246 Germany
    • Universitaetsklinikum Jena
    • Jena 07747 Germany
    • Universitaetsklinikum Magdeburg A.o.R.
    • Magdeburg 39120 Germany
    • Klinikum rechts der Isar der Technischen Universitat
    • Muenchen 81675 Germany
    • Krankenhaus der Barmherzigen Brueder Trier
    • Trier 54292 Germany
    • Universitaetsklinikum Tuebingen
    • Tuebingen 72076 Germany
    • Cork University Hospital
    • Cork Ireland
    • Adelaide & Meath Hospital (Incl NCH)
    • Dublin 00024 Ireland
    • University College Hospital Galway
    • Galway H91YR71 Ireland
    • University Hospital Limerick
    • Limerick V94 F858 Ireland
    • University Hospital Waterford
    • Waterford X91ER8E Ireland
    • Soroka Medical Center
    • Be'er Sheva 8410101 Israel
    • Rambam Health Care Campus
    • Haifa 31096 Israel
    • Meir Medical Center
    • Kfar Saba 4428164 Israel
    • Rabin Medical Center
    • Petach-Tikwa 49100 Israel
    • Chaim Sheba Medical Center
    • Ramat Gan 52621 Israel
    • Sourasky Medical Center
    • Tel Aviv 6423906 Israel
    • Assaf Harofeh Medical Center
    • Zerifin 70300 Israel
    • Medical Oncology Ospedale San Donato
    • Arezzo 52100 Italy
    • Istituto Tumori Giovanni Paolo II
    • Bari 70124 Italy
    • Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST
    • Meldola 47014 Italy
    • Istituto Nazionale dei Tumori
    • Milan 20133 Italy
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
    • Napoli 80131 Italy
    • Istituto Oncologico Veneto
    • Padova 35128 Italy
    • Nagoya University Hospital
    • Nagoya Aichi 466-8560 Japan
    • National Cancer Center Hospital East
    • Kashiwa Chiba 277-8577 Japan
    • University of Tsukuba Hospital
    • Tsukuba Ibaraki 305-8576 Japan
    • Nara Medical University Hospital
    • Kashihara Nara 634-8522 Japan
    • Kindai University Hospital
    • Osakasayama Osaka 589-8511 Japan
    • Yamaguchi University Hospital
    • Ube Yamaguchi 755-8505 Japan
    • Tokushima University Hospital
    • Tokushima 770-8503 Japan
    • Medical Hospital, Tokyo Medical And Dental University
    • Tokyo 113-8519 Japan
    • The Cancer Institute Hospital of JFCR
    • Tokyo 135-8550 Japan
    • Chungnam National University Hospital
    • Daejeon 35015 Korea, Republic of
    • Seoul National University Hospital
    • Seoul 03080 Korea, Republic of
    • Severance Hospital Yonsei University Health System
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 06351 Korea, Republic of
    • Amphia Ziekenhuis
    • Breda Brabant 4819EV Netherlands
    • Antoni van Leeuwenhoek Ziekenhuis
    • Amsterdam 1066 CX Netherlands
    • VU University Medical Center
    • Amsterdam 1081 HV Netherlands
    • Catharina Ziekenhuis
    • Eindhoven 5623 EJ Netherlands
    • University Medical Center Groningen
    • Groningen 9713 GZ Netherlands
    • Erasmus MC
    • Rotterdam 3075 EA Netherlands
    • Beskidzkie Centrum Onkologii im. Jana Pawla II
    • Bielsko-Biala 43-300 Poland
    • Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej
    • Jelenia Góra 58-506 Poland
    • Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego
    • Katowice 40-514 Poland
    • Europejskie Centrum Zdrowia Otwock
    • Otwock 05-400 Poland
    • Urologica Praktyka Lekarska Adam Marcheluk
    • Siedlce 08-110 Poland
    • Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
    • Szczecin 70-111 Poland
    • Magodent Szpital Elblaska
    • Warszawa 01-748 Poland
    • Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne
    • Warszawa 02 616 Poland
    • Leningrad Regional Oncology Dispensary
    • Saint Petersburg Leningrad Region, Vsevolozhsky District 188663 Russian Federation
    • Ivanovo Regional Oncology Dispensary
    • Ivanovo 153013 Russian Federation
    • N.N. Blokhin NMRCO
    • Moscow 115478 Russian Federation
    • Russian Scientific Center of Roentgenoradiology
    • Moscow 117997 Russian Federation
    • National Medical Research Radiological Centre
    • Moscow 125284 Russian Federation
    • Ryazan Regional Clinical Oncology Dispensary
    • Ryazan 390046 Russian Federation
    • Pokrovskaya City Hospital
    • Saint Petersburg 199106 Russian Federation
    • Clinic of Bashkortostan State Medical University
    • Ufa 450000 Russian Federation
    • Hospital Teresa Herrera - Chuac
    • A Coruña 15006 Spain
    • Hospital Infanta Cristina
    • Badajoz 06080 Spain
    • Hospital General Universitari Vall d Hebron
    • Barcelona 08035 Spain
    • ICO L Hospitalet
    • Hospitalet de Llobregat 08908 Spain
    • Hospital Lucus Augusti
    • Lugo 27003 Spain
    • Xarxa Assistencial Universitaria Manresa
    • Manresa 08243 Spain
    • Consorci Hospitalari Parc Tauli de Sabadell
    • Sabadell 08208 Spain
    • Hospital Virgen del Rocio
    • Sevilla 41013 Spain
    • Taipei Veterans General Hospital
    • Taipei Beitou 112 Taiwan
    • Chang Gung Medical Foundation - Kaohsiung
    • Kaohsiung 833 Taiwan
    • China Medical University Hospital
    • Taichung 40447 Taiwan
    • National Cheng Kung University Hospital
    • Tainan 704 Taiwan
    • National Taiwan University Hospital
    • Taipei 100 Taiwan
    • MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov
    • Dnipropetrovsk 49005 Ukraine
    • Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC
    • Dnipropetrovsk 49102 Ukraine
    • Kharkiv Regional Clinical Oncology Center
    • Kharkiv 61000 Ukraine
    • Kyiv City Clinical Oncology Center
    • Kyiv 03115 Ukraine
    • MI Odessa Regional Oncological Centre
    • Odesa 65055 Ukraine
    • RMI Sumy Regional Clinical Oncology Dispensary
    • Sumy 40022 Ukraine
    • Royal Marsden NHS Trust
    • Sutton Surrey SM2 5PT United Kingdom
    • Beatson Institute of Cancer Research
    • Glasgow G120YN United Kingdom
    • Barts Health NHS Trust - St Bartholomew's Hospital
    • London EC1A 7BE United Kingdom
    • Royal Free London NHS Foundation Trust
    • London NW3 2QG United Kingdom
    • Imperial College Healthcare NHS Trust
    • London W6 8RF United Kingdom
    • Plymouth Hospitals NHS Trust
    • Plymouth PL6 8DH United Kingdom
    • Sunderland Royal Hospital
    • Sunderland SR4 7TP United Kingdom

    View trial on ClinicalTrials.gov


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    Published January 21, 2018
  • A Phase 3 Randomized, Double-blind, Multi-center Study of Adjuvant Nivolumab Versus Placebo in Subjects With High Risk Invasive Urothelial Carcinoma (CheckMate 274: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 274)

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    A Phase 3 Randomized, Double-blind, Multi-center Study of Adjuvant Nivolumab Versus Placebo in Subjects With High Risk Invasive Urothelial Carcinoma (CheckMate 274: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 274)


    Condition: Various Advanced Cancer

    Intervention:

    • Biological: Nivolumab
    • Other: Placebo

    Purpose: The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02632409

    Sponsor: Bristol-Myers Squibb

    Primary Outcome Measures:

    • Measure: Disease free survival (DFS)
    • Time Frame: Approximately 5 years after the first subject is randomized
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall survival (OS)
    • Time Frame: Approximately 5 years after the first subject is randomized
    • Safety Issue:
    • Measure: Non-Urothelial track recurrence free survival (NUTRFS)
    • Time Frame: Approximately 5 years after the first subject is randomized
    • Safety Issue:
    • Measure: Disease specific survival (DSS)
    • Time Frame: Approximately 5 years after the first subject is randomized
    • Safety Issue:

    Estimated Enrollment: 700

    Study Start Date: February 11, 2016

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis
    • Must have had radical surgical resection (e.g. radical cystectomy), performed within the last 120 days
    • Must have disease free status as determined by imaging within 4 weeks of dosing
    • Tumor tissue must be provided for biomarker analysis
    • Patients who have not received prior neoadjuvant cisplatin chemotherapy must be ineligible for or refuse cisplatin-based adjuvant chemotherapy

    Exclusion Criteria:

    • Partial bladder or partial kidney removal (eg, partial cystectomy or partial nephrectomy)
    • Secondary Treatment (eg, adjuvant systemic chemotherapy for bladder cancer) following surgical removal of bladder cancer
    • Subjects with active, known or suspected autoimmune disease
    • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
    • Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 day of study drug administration
    • Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

    Contact:

    • Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:

    Locations:

    • Alaska Urological Institute dba Alaska Clinical Research Center
    • Anchorage Alaska 99503 United States
    • Arizona Oncology Associates
    • Tucson Arizona 85711 United States
    • University Of California San Francisco-Fresno
    • Clovis California 93611 United States
    • University Of California - Davis
    • Sacramento California 95817 United States
    • California Pacific Medical Center
    • San Francisco California 94115 United States
    • Rocky Mountain Cancer Centers
    • Lakewood Colorado 80228 United States
    • University Of Florida
    • Gainesville Florida 32610 United States
    • Mount Sinai Comprehensive Cancer Center
    • Miami Beach Florida 33140 United States
    • H. Lee Moffitt Cancer Center
    • Tampa Florida 33612 United States
    • Loyola University Medical Center
    • Maywood Illinois 60153 United States
    • Ft. Wayne Med Onco-Hema Inc
    • Fort Wayne Indiana 46804 United States
    • Tulane University
    • New Orleans Louisiana 70112 United States
    • Cancer & Hematology Centers Of Western Michigan
    • Grand Rapids Michigan 49503 United States
    • Fairview Health Services
    • Burnsville Minnesota 55337 United States
    • Mayo Clinic
    • Rochester Minnesota 55905 United States
    • GU Research Network, LLC
    • Omaha Nebraska 68130 United States
    • Comprehensive Cancer Centers of Nevada
    • Las Vegas Nevada 89148 United States
    • New York Oncology Hematology, P.C.
    • Albany New York 12208 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • Winthrop University Hospital
    • Mineola New York 11501 United States
    • Mount Sinai Medical Center
    • New York New York 10029 United States
    • Memorial Sloan Kettering Nassau
    • New York New York 10065 United States
    • University Of North Carolina
    • Chapel Hill North Carolina 27599-7305 United States
    • Local Institution
    • Durham North Carolina 27708 United States
    • Providence Portland Medical Center
    • Portland Oregon 97213 United States
    • Oregon Health & Science University
    • Portland Oregon 97239 United States
    • Northwest Cancer Specialists, Pc
    • Tigard Oregon 97223 United States
    • Lehigh Valley Health Network
    • Allentown Pennsylvania 18103 United States
    • Allegheny General Hospital
    • Pittsburgh Pennsylvania 15212 United States
    • University of Pittsburgh Cancer Institute Cancer Services
    • Pittsburgh Pennsylvania 15232 United States
    • Carolina Urologic Research Center
    • Myrtle Beach South Carolina 29572 United States
    • Erlanger Oncology & Hematology - Univ. of TN
    • Chattanooga Tennessee 37403 United States
    • Virginia Oncology Associates
    • Virginia Beach Virginia 23456 United States
    • COIBA
    • Berazategui Buenos Aires 1880 Argentina
    • Instituto Medico Especializado Alexander Fleming
    • Capital Federal Buenos Aires 1426 Argentina
    • Hospital Italiano De Buenos Aires
    • Ciudad Autonoma De Buenos Aire Buenos Aires 1181 Argentina
    • Hospital Britanico De Buenos Aires
    • Ciudad Autonoma de BuenosAires Buenos Aires C1280AEB Argentina
    • Clinica Viedma S.A.
    • Viedma RIO Negro 8500 Argentina
    • Centro Para La Atencion Integral Del Paciente Oncologico
    • San Miguel De Tucuman Tucuman 4000 Argentina
    • Liverpool Hospital
    • Liverpool New South Wales 2170 Australia
    • Royal North Shore Hospital
    • St. Leonards New South Wales 2065 Australia
    • Calvary Mater Newcastle
    • Waratah New South Wales 2298 Australia
    • Frankston Hospital
    • Frankston Victoria 3199 Australia
    • St John of God Murdoch Hospital
    • Perth Western Australia 6150 Australia
    • Lyell McEwin Hospital
    • Elizabeth Vale 5112 Australia
    • Krankenhaus der Elisabethinen Linz GmbH
    • Linz 4010 Austria
    • Salzburger Landeskliniken Lkh
    • Salzburg 5020 Austria
    • Akh Wien
    • Vienna 1090 Austria
    • AKH Allgemeines Krankenhaus Wien
    • Wien 1090 Austria
    • Local Institution
    • Hasselt 3500 Belgium
    • Chu De Liege
    • Liege 4000 Belgium
    • Local Institution
    • Roeselare 8800 Belgium
    • Associacao Hospital de Caridade Ijui
    • Ijui RIO Grande DO SUL 98700-000 Brazil
    • Hospital Sao Lucas Da Pucrs
    • Porto Alegre RIO Grande DO SUL 90610-000 Brazil
    • Fundacao Pio Xii Hosp Cancer De Barretos
    • Barretos SAO Paulo 14780-070 Brazil
    • Local Institution
    • Cerqueira Cesar SAO Paulo 01246-000 Brazil
    • Ibcc - Inst. Bras. De Controle De Cancer
    • S?o Paulo SAO Paulo 03102-006 Brazil
    • Inca - Instituto Nacional Do Cancer
    • Rio De Janeiro 20231-050 Brazil
    • Local Institution
    • Edmonton Alberta T6G 1Z2 Canada
    • Mcgill University Health Center - Royal Victoria Hospital
    • Montreal Quebec H4A 3J1 Canada
    • Centre integre universitaire de sante et de service sociaux de l'estrie - CHUS
    • Sherbrooke Quebec J1H 5N4 Canada
    • Centre Hospitalier De L'Universite De Montreal
    • Montreal H2X 0A9 Canada
    • Fundacion Arturo Lopez Perez
    • Santiago Metropolitana Chile
    • Instituto Oncologico Clinica Renaca
    • Vina Del Mar Valparaiso 2540364 Chile
    • Clinica Alemana de Temuco S.A.
    • Temuco 4810297 Chile
    • Local Institution
    • Beijing Beijing 100001 China
    • Local Institution
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    • Administradora Del Country S.A. - Clinica Del Country
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    • Floridablanca 681004 Colombia
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    • Stuttgart 70174 Germany
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    • Badalona-barcelona 08916 Spain
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    • Madrid 28007 Spain
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    • Madrid 28034 Spain
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    • Madrid 28041 Spain
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    • Santander 39008 Spain
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    • Cardiff Cardiganshire CF142TL United Kingdom
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    • London Greater London NW3 2QG United Kingdom
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    • Manchester Greater Manchester M20 4BX United Kingdom
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    • Edinburgh Midlothian EH4 2XU United Kingdom
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    • Cancer Research Centre
    • Sheffield Yorkshire S10 2SJ United Kingdom
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    • London SE1 9RT United Kingdom
    • Local Institution
    • London SW3 6JJ United Kingdom

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published May 18, 2017
  • A Phase 3, Multicenter, Multinational, Randomized, Open-label, Parallel-arm Study Of Avelumab* (msb0010718c) Plus Best Supportive Care Versus Best Supportive Care Alone As A Maintenance Treatment In Patients With Locally Advanced Or Metastatic Urothelial

    {{header-clinical-trials-navigation}}

    A Phase 3, Multicenter, Multinational, Randomized, Open-label, Parallel-arm Study Of Avelumab (MSB0010718C) Plus Best Supportive Care Versus Best Supportive Care Alone As A Maintenance Treatment In Patients With Locally Advanced Or Metastatic Urothelial Cancer Whose Disease Did Not Progress After Completion Of First-line Platinum-containing Chemotherapy


    Condition: Urothelial Cancer

    Intervention:

    • Biological: Avelumab
    • Other: Best Supportive Care

    Purpose: The main purpose of this study is to compare maintenance treatment with avelumab plus best supportive care (BSC) with BSC alone, to determine if avelumab has an effect on survival in patients with locally advanced or metastatic urothelial cancer that did not worsen during or following completion of first-line chemotherapy.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02603432

    Sponsor: Pfizer

    Primary Outcome Measures:

    • Measure: Overall Survival
    • Time Frame: Up to approximately 40 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Progression-Free Survival
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Objective Response
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Duration of Response
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Disease Control
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Cmax
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Ctrough
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Incidence of Anti-Drug Antibody
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Tumor Tissue Biomarkers
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: Functional Assessment of Cancer Therapy - Bladder Cancer
    • Time Frame: Up to approximately 40 months
    • Safety Issue:
    • Measure: EuroQoL EQ-5D
    • Time Frame: Up to approximately 40 months
    • Safety Issue:

    Estimated Enrollment: 668

    Study Start Date: April 28, 2016

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium
    • Stage IV disease at the start of first-line chemotherapy
    • Measurable disease (per RECIST v1.1) prior to the start of first-line chemotherapy
    • Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin
    • No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )

    Exclusion Criteria:

    • Prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization
    • Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
    • Persisting toxicity related to prior therapy (Grade >1 NCI CTCAE v4.0); however, alopecia, sensory neuropathy (Grade 2 or less), or other (Grade 2 or less) adverse events not constituting a safety risk based on the investigator's judgement are acceptable.
    • Patients with known symptomatic central nervous system (CNS) metastases requiring steroids
    • Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.

    Contact:

    • Pfizer CT.gov Call Center
    • 1-800-718-1021

    Locations:

    • Anschutz Cancer Center Pavilion Pharmacy
    • Aurora Colorado 80045 United States
    • University of Colorado Cancer Center
    • Aurora Colorado 80045 United States
    • University of Colorado Denver, CTO (CTRC)
    • Aurora Colorado 80045 United States
    • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
    • Aurora Colorado 80045 United States
    • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
    • Aurora Colorado 80045 United States
    • Smilow Cancer Hospital at Yale New Haven
    • New Haven Connecticut 06510 United States
    • Smilow Cancer Hospital at Yale-New Haven
    • New Haven Connecticut 06510 United States
    • Emory University Hospital
    • Atlanta Georgia 30322 United States
    • Investigational Drug Service- Emory University
    • Atlanta Georgia 30322 United States
    • The Emory Clinic
    • Atlanta Georgia 30322 United States
    • Winship Cancer Institute, Emory University
    • Atlanta Georgia 30322 United States
    • Massachusetts General Hospital
    • Boston Massachusetts 02114 United States
    • University of Minnesota Medical Center
    • Minneapolis Minnesota 55455 United States
    • University of Minnesota
    • Minneapolis Minnesota 55455 United States
    • Cleveland Clinic Foundation
    • Cleveland Ohio 44195 United States
    • Cleveland Clinic Taussing Cancer Center
    • Cleveland Ohio 44195 United States
    • Inova Schar Cancer Institute
    • Fairfax Virginia 22031 United States
    • Seattle Cancer Care Alliance
    • Seattle Washington 98109-1023 United States
    • Seattle Cancer Care Alliance
    • Seattle Washington 98109 United States
    • University of Washington Medical Center
    • Seattle Washington 98195 United States
    • Centro de Investigacion Pergamino S.A.
    • Pergamino Buenos Aires B2700CPM Argentina
    • Fundación CENIT para la Investigación en Neurociencias
    • Caba C1125ABD Argentina
    • GP Diagnostico SRL
    • La Rioja 5300 Argentina
    • Hospital Regional Dr. Enrique Vera Barros
    • La Rioja 5300 Argentina
    • Instituto del Diagnostico
    • La Rioja 5300 Argentina
    • Centro Oncologico Riojano Integral (Cori)
    • La Rioja F5300COE Argentina
    • Chris O'Brien Lifehouse Pharmacy
    • Camperdown New South Wales 2050 Australia
    • Chris O'Brien Lifehouse
    • Camperdown New South Wales 2050 Australia
    • Concord Hospital
    • Concord New South Wales 2139 Australia
    • Concord Repatriation General Hospital
    • Concord New South Wales 2139 Australia
    • Ramsay Pharmacy
    • Kogarah New South Wales 2217 Australia
    • St George Private Hospital
    • Kogarah New South Wales 2217 Australia
    • Epic Pharmacy
    • Lismore New South Wales 2480 Australia
    • Macquarie University Hospital Pharmacy
    • Macquarie University New South Wales 2109 Australia
    • Macquarie University
    • Macquarie University New South Wales 2109 Australia
    • Clinical Trials Pharmacy
    • St Leonards New South Wales 2065 Australia
    • Northern Sydney Cancer Centre
    • St Leonards New South Wales 2065 Australia
    • Royal North Shore Hospital
    • St Leonards New South Wales 2065 Australia
    • The Tweed Hospital
    • Tweed Heads New South Wales 2485 Australia
    • Icon Cancer Care Wesley
    • Auchenflower Queensland 4066 Australia
    • River City Pharmacy
    • Auchenflower Queensland 4066 Australia
    • Oncology Pharmacy
    • Birtinya Queensland 4575 Australia
    • Sunshine Coast University Hospital
    • Birtinya Queensland 4575 Australia
    • Icon Cancer Care Chermside
    • Chermside Queensland 4032 Australia
    • The Townsville Hospital
    • Douglas Queensland 4814 Australia
    • Slade Health
    • Geebung Queensland 4034 Australia
    • Icon Cancer Care South Brisbane
    • South Brisbane Queensland 4101 Australia
    • Icon Cancer Care
    • South Brisbane Queensland 4101 Australia
    • Icon Cancer Foundation
    • South Brisbane Queensland 4101 Australia
    • Icon Cancer Care Southport
    • Southport Queensland 4215 Australia
    • Flinders Medical Centre
    • Bedford Park South Australia 5042 Australia
    • SA Pharmacy, Level 3 Pharmacy
    • Bedford Park South Australia 5042 Australia
    • Adelaide Cancer Centre
    • Kurralta Park South Australia 5037 Australia
    • Ashford Cancer Centre Research
    • Kurralta park South Australia 5037 Australia
    • Cancer Care SA Pty Ltd
    • Kurralta Park South Australia 5037 Australia
    • Icon Cancer Care SA trading as Icon Pharmacy Adelaide
    • Kurralta Park South Australia 5037 Australia
    • Queen Elizabeth Hospital
    • Woodville South South Australia 5011 Australia
    • The Queen Elizabeth Hospital
    • Woodville South South Australia 5011 Australia
    • Lake Imaging
    • Ballarat Victoria 3350 Australia
    • Ballarat Oncology & Haematology Services
    • Ballarat Victoria 3355 Australia
    • Box Hill Hospital
    • Box Hill Victoria 3128 Australia
    • Eastern Health Clinical School
    • Box Hill Victoria 3128 Australia
    • Monash Medical Centre
    • Clayton Victoria 3168 Australia
    • Monash Cancer Centre
    • East Bentleigh Victoria 3165 Australia
    • Moorabbin Radiology
    • East Bentleigh Victoria 3165 Australia
    • Ballarat Day Procedure Centre
    • Wendouree Victoria 3355 Australia
    • Nova Pharmacy
    • Wendouree Victoria 3355 Australia
    • Slade Health
    • West Melbourne Victoria 3003 Australia
    • SKG Radiology
    • Murdoch Western Australia 6050 Australia
    • Fiona Stanley Hospital
    • Murdoch Western Australia 6150 Australia
    • St John of God Murdoch Hospital
    • Murdoch Western Australia 6150 Australia
    • AZ Klina - Apotheek
    • Brasschaat 2930 Belgium
    • AZ Klina
    • Brasschaat 2930 Belgium
    • Hôpital Erasme
    • Brussels 1070 Belgium
    • Hôpital Erasme
    • Bruxelles 1070 Belgium
    • UZ Gent
    • Gent 9000 Belgium
    • AZ Groeninge
    • Kortrijk 8500 Belgium
    • CHU de Liège
    • Liège 4000 Belgium
    • GZA Sint-Augustinus
    • Wilrijk 2610 Belgium
    • Hospital da Bahia
    • Salvador BA 41820-011 Brazil
    • CENOB Centro de Oncologia da Bahia S/S Ltda. / Oncovida
    • Salvador BA 41820-021 Brazil
    • Associação Educadora São Carlos - AESC / Hospital Giovanni Battista - HGB
    • Porto Alegre RIO Grande DO SUL 90470-340 Brazil
    • Instituto Nacional de Câncer - INCA
    • Rio de Janeiro RJ 20230-130 Brazil
    • Coordenação de Pesquisa Clínica do Instituto Nacional de Cancer - INCA
    • Rio de Janeiro RJ 20231-050 Brazil
    • Hospital Pró-Cardíaco
    • Rio de Janeiro RJ 22280-020 Brazil
    • Instituto COI de Pesquisa, Educação e Gestão/COI Clínicas Oncológicas Integradas SA - Farmácia
    • Rio de Janeiro RJ 22793-080 Brazil
    • Instituto COI de Pesquisa, Educação e Gestão/COI Clínicas Oncológicas Integradas SA
    • Rio de Janeiro RJ 22793-080 Brazil
    • Associação Hospital de Caridade Ijuí / Hospital de Caridade de Ijuí
    • Ijuí RS 98700-000 Brazil
    • Hospital Nossa Senhora da Conceição S/A
    • Porte Alegre RS 91350-200 Brazil
    • Associação Educadora São Carlos - AESC / Hospital Giovanni Battista - HGB - Farmácia Oncológica
    • Porto Alegre RS 90470-340 Brazil
    • Associação Educadora São Carlos - AESC / Hospital Giovanni Battista - HGB - Pesquisa Clínica
    • Porto Alegre RS 90470-340 Brazil
    • Uniao Brasileira de Educacao e Assistencia / Hospital Sao Lucas da PUCRS
    • Porto Alegre RS 90610-000 Brazil
    • Hospital Mãe de Deus
    • Porto Alegre RS 90880-481 Brazil
    • Hospital Nossa Senhora da Conceição S/A
    • Porto Alegre RS 91350-200 Brazil
    • Fundação FPio XII Barretos
    • Barretos SP 14784-400 Brazil
    • Fundação Pio XII Barretos
    • Barretos SP 14784-400 Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
    • Sao Jose do Rio Preto SP 15090-000 Brazil
    • Fundacao Faculdade de Medicina / Instituto do Cancer do Estado de Sao Paulo - ICESP
    • Sao Paulo SP 01246-000 Brazil
    • Hospital Alemao Oswaldo Cruz
    • Sao Paulo SP 01323-903 Brazil
    • Hospital das Clinicas da Faculdade de Medicina da USP - HCFMUSP
    • Sao Paulo SP 05403-900 Brazil
    • Centro Integrado de Pesquisa Clinica - CIP
    • São José do Rio Preto SP 15090-000 Brazil
    • Sociedade Beneficente de Senhoras Hospital Sírio Libanês
    • São Paulo SP 01308-050 Brazil
    • Sociedade Beneficente de Senhoras Hospital Sírio Libanês
    • São Paulo SP 01308-060 Brazil
    • Hospital Israelita Albert Einstein - SP
    • São Paulo SP 05652-900 Brazil
    • William Osler Health System
    • Brampton Ontario L6R 3J7 Canada
    • Princess Margaret Cancer Centre
    • Toronto Ontario M5G 2M9 Canada
    • Hôpital Notre-Dame du CHUM, Oncology Pharmacy
    • Montreal Quebec H2L 4M1 Canada
    • Oncology Center, Hôpital Notre-Dame du Centre Hospitalier de l'Université de Montréal (CHUM)
    • Montreal Quebec H2L 4M1 Canada
    • Fakultni nemocnice u sv. Anny v Brne
    • Brno Ceska Republika 656 91 Czechia
    • Fakultni nemocnice Brno
    • Brno 625 00 Czechia
    • Fakultni nemocnice u sv. Anny v Brne
    • Brno 656 91 Czechia
    • Fakultni nemocnice u sv.Anny v Brne
    • Brno 656 91 Czechia
    • Nemocnice Horovice, NH Hospital a.s.
    • Horovice 268 31 Czechia
    • Nemocnice Horovice
    • Horovice 268 31 Czechia
    • Lekarna Multiscan Pharma s.r.o.
    • Pardubice 532 03 Czechia
    • Nemocnice Na Bulovce (IP Shipment)
    • Praha 8 180 81 Czechia
    • Nemocnice Na Bulovce
    • Praha 8 180 81 Czechia
    • Aalborg Universitetshospital
    • Aalborg 9000 Denmark
    • Aarhus Universitetshospital
    • Aarhus C 8000 Denmark
    • Aarhus Universitetshospital
    • Aarhus N 8200 Denmark
    • CT-Klinikken A/S
    • Aarhus N 8200 Denmark
    • Rigshospitalet, Onkologisk Klinik, afsnit 5073
    • Copenhagen OE 2100 Denmark
    • Herlev Hospital
    • Herlev 2730 Denmark
    • Rigshospitalet
    • København Ø 2100 Denmark
    • Odense Universitetshospital
    • Odense C 5000 Denmark
    • Odense Universitetshospital
    • Odense 5000 Denmark
    • Institut de cancérologie de l'Ouest - Site Paul Papin
    • Angers Cedex 02 49055 France
    • Institut de cancérologie de l'Ouest - Site Paul Papin
    • Angers 49100 France
    • Centre d'Oncologie et de Radiothérapie du Pays-Basque
    • Bayonne 64100 France
    • Clinique CAPIO Belharra
    • Bayonne 64100 France
    • Hôpital Jean Minjoz
    • BESANCON cedex 25030 France
    • CHU Besançon
    • Besançon 25030 France
    • Hôpital Henri Mondor
    • CRÉTEIL Cedex 94010 France
    • Hôpital Privé Toulon-Hyères - Clinique Sainte Marguerite
    • Hyères 83400 France
    • Clinique Victor Hugo
    • Le Mans 72015 France
    • Centre Oscar Lambret
    • Lille cedex 59020 France
    • Centre Oscar Lambret
    • Lille 59000 France
    • Centre Leon Berard
    • Lyon cedex 8 69373 France
    • Centre Léon Berard
    • LYON cedex 8 69373 France
    • Hopital La Conception
    • Marseille cedex 5 13285 France
    • Institut Paoli Calmettes
    • Marseille Cedex 9 13273 France
    • Institut Paoli Calmettes
    • Marseille 13009 France
    • Hopital de La Timone
    • Marseille 13385 cedex 05 France
    • Hopital de La Timone
    • Marseille 13385 France
    • CHU Nimes - Institut de Cancerologie du Gard
    • Nimes Cedex 9 30029 France
    • CHU Nimes
    • Nimes Cedex 9 30029 France
    • CHU Nimes - Hopital Caremeau
    • Nimes 30000 France
    • Groupe Hospitalier Pitié Salpêtrière
    • PARIS cedex 13 75651 France
    • Groupe Hospitalier Pitié Salpêtrière
    • Paris 75013 France
    • Centre Eugene Marquis
    • Rennes Cedex 35042 France
    • CHU de Rouen - Hôpital Charles Nicolle
    • Rouen 76031 France
    • Institut de cancérologie de l'Ouest - Centre René Gauducheau
    • Saint Herblain cedex 44805 France
    • Centre de Radiothérapie - Clinique Sainte Anne
    • Strasbourg 67000 France
    • Clinique Sainte Anne
    • Strasbourg 67000 France
    • Hopital FOCH
    • Suresnes 92150 France
    • Hopital Foch
    • Suresnes 92151 France
    • Institut Gustave Roussy
    • Villejuif cedex 94805 France
    • Institut Gustave Roussy
    • Villejuif 94805 France
    • IASO General Hospital
    • Athens Cholargos 15562 Greece
    • Sotiria General Chest Disease Hospital
    • Athens 11527 Greece
    • Alexandra General Hospital, Oncology Department
    • Athens 11528 Greece
    • University General Hospital of Patras, Division of Oncology
    • Patra 26504 Greece
    • EUROMEDICA General Clinic of Thessaloniki
    • Thessaloniki 546 45 Greece
    • Department of Clinical Oncology
    • Hong Kong Hong Kong
    • Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont
    • Budapest 1076 Hungary
    • Péterfy Sándor utcai Kórház-Rendelőintézet és Baleseti Központ
    • Budapest 1076 Hungary
    • Kaposvári Egyetem Egészségügyi Centrum
    • Kaposvár 7400 Hungary
    • Somogy Megyei Kaposi Mór Oktató Kórház
    • Kaposvár 7400 Hungary
    • Dr RML Hospital & PGI MER
    • New Delhi Delhi 110001 India
    • CIMS Cancer, Care Institute of Medical Sciences, CIMS Hospital
    • Ahmedabad Gujarat 380060 India
    • Muljibhai Patel Urological Hospital
    • Nadiad Gujarat 387001 India
    • Meditrina Institute Of Medical Sciences
    • Nagpur Maharashtra 440010 India
    • Sahyadri Speciality Hospital
    • Pune Maharashtra 411004 India
    • Apollo Hospitals
    • Hyderabad Telangana 500096 India
    • Medica Superspecialty hospital
    • Kolkata WEST Bengal 700099 India
    • Rajiv Gandhi Cancer Institute and Research Centre
    • Delhi 110085 India
    • Hadassah University Hospital
    • Kiryat Hadassah Jerusalem 91120 Israel
    • The Chaim Sheba Medical Center
    • Tel-Hashomer Ramat - GAN 5265601 Israel
    • Assaf Harofe MC
    • Beer Yaakov 70300 Israel
    • Rambam Health Care Campus
    • Haifa 31096 Israel
    • Rabin Medical Center
    • Petach Tikva 49100 Israel
    • The Chaim Sheba Medical Center
    • Ramat - Gan 5265601 Israel
    • Farmacia Ospedaliera
    • Candiolo (torino) 10060 Italy
    • AOU Ospedali Riuniti di Ancona
    • Torrette Ancona 60126 Italy
    • Farmacia Oncologica
    • Meldola Forli-cesena 47014 Italy
    • Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori
    • Meldola Forll-cesena 47014 Italy
    • Farmacia Studi Clinici
    • Rozzano Milan 20089 Italy
    • Istituto Clinico Humanitas
    • Rozzano Milan 20089 Italy
    • AUSL della Romagna - RAVENNA, Presidio Ospedaliero di Faenza
    • Faenza Ravenna 48018 Italy
    • Presidio Ospedaliero di Lugo
    • Lugo Ravenna 48022 Italy
    • Fondazione del Piemonte per l'Oncologia - IRCCS Candiolo
    • Candiolo Torino 10060 Italy
    • Presidio Ospedaliero San Donato
    • Arezzo Toscana 52100 Italy
    • Farmacia Ospedaliera
    • Arezzo 52100 Italy
    • Centro di Riferimento Oncologico - IRCCS
    • Aviano (PN) 33081 Italy
    • S.O.C. di Farmacia
    • Aviano (PN) 33081 Italy
    • Azienda Ospedaliero-Universitaria Policlinico S.Orsola Malpighi
    • Bologna 40138 Italy
    • U.O. Farmacia Clinica - IDS
    • Bologna 40138 Italy
    • IRCCS AOU San Martino - IST
    • Genova 16132 Italy
    • U.O.C. Farmacia
    • Genova 16132 Italy
    • Fondazione IRCCS Istituto Nazionale Dei Tumori
    • Milan 20133 Italy
    • SC Farmacia
    • Milan 20133 Italy
    • Instituto Europeo di Oncologia
    • Milan 20141 Italy
    • Servizio di Farmacia
    • Milan 20141 Italy
    • Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
    • Naples 80131 Italy
    • UOSC Farmacia
    • Naples 80131 Italy
    • Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS Fondazione Giovanni Pascale
    • Napoli 80131 Italy
    • S.C. Farmacia Ospedaliera
    • Napoli 80131 Italy
    • Azienda Ospedaliero-Universitaria Maggiore della Carita
    • Novara 28100 Italy
    • S.C. Farmacia Ospedaliera
    • Novara 28100 Italy
    • A.O.U. Pisana Ospedale S. Chiara
    • Pisa 56126 Italy
    • U.O. Farmacia Ospedaliera
    • Pisa 56126 Italy
    • Presidio Ospedaliero di Ravenna
    • Ravenna 48121 Italy
    • Servizio Farmacia Ospedaliera - Farmacia Oncologia
    • Ravenna 48121 Italy
    • Azienda Ospedaliera San Camillo Forlanini_Oncologia Medica
    • Rome 00152 Italy
    • U.O.C. Farmacia
    • Rome 00152 Italy
    • Azienda Ospedaliera S. Maria di Terni
    • Terni 05100 Italy
    • S.C. Farmacia Interna
    • Terni 05100 Italy
    • Nagoya University Hospital
    • Nagoya Aichi 466-8560 Japan
    • Hirosaki University School of Medicine & Hospital
    • Hirosaki Aomori 036-8563 Japan
    • National Hospital Organization Shikoku Cancer Center
    • Matsuyama Ehime 791-0280 Japan
    • Gunma Prefectural Cancer Center
    • Ota Gunma 373-8550 Japan
    • National Hospital Organization hokkaido Cancer Center
    • Sapporo, Hokkaido 0030804 Japan
    • Hokkaido University Hospital
    • Sapporo Hokkaido 060-8648 Japan
    • Kobe City Medical Center General Hospital
    • Kobe-city Hyogo 650-0047 Japan
    • Tsukuba Medical Center Hospital
    • Tsukuba Ibaraki 305-8558 Japan
    • Iwate Medical University Hospital
    • Morioka Iwate 020-8505 Japan
    • National Hospital Organization Sagamihara National Hospital
    • Sagamihara Kanagawa 252-0392 Japan
    • Kanagawa Cancer Center
    • Yokohama Kanagawa 241-8515 Japan
    • Kindai University Hospital
    • Osakasayama Osaka 589-8511 Japan
    • Saitama Medical University International Medical Center
    • Hidaka Saitama 350-1298 Japan
    • Dokkyo Medical University Saitama Medical Center
    • Koshigaya Saitama 343-8555 Japan
    • Hamamatsu University School of Medicine, University Hospital
    • Hamamatsu Shizuoka 431-3192 Japan
    • Nihon University Itabashi Hospital
    • Itabashi-ku Tokyo 173-8610 Japan
    • Japanese Foundation For Cancer Research Cancer Institute Hospital
    • Koto-ku Tokyo 135-8550 Japan
    • Keio University Hospital
    • Shinjuku-Ku Tokyo 160-8582 Japan
    • Yamaguchi University Hospital
    • Ube Yamaguchi 755-8505 Japan
    • Chiba Cancer Center
    • Chiba 260-8717 Japan
    • National Hospital Organization Kyushu Cancer Center
    • Fukuoka 811-1395 Japan
    • Kyushu University Hospital
    • Fukuoka 812-8582 Japan
    • Hiroshima City Hiroshima Citizens Hospital
    • Hiroshima 730-8518 Japan
    • Kagoshima University Hospital
    • Kagoshima 890-8520 Japan
    • National Hospital Organization Kumamoto Medical Center
    • Kumamoto 860-0008 Japan
    • University Hospital, Kyoto Prefectural University of Medicine
    • Kyoto 602-8566 Japan
    • Niigata University Medical & Dental Hospital
    • Niigata 951-8520 Japan
    • Osaka City University Hospital
    • Osaka 545-8586 Japan
    • Tokushima University Hospital
    • Tokushima 770-8503 Japan
    • Yamagata University Hospital
    • Yamagata 990-9585 Japan
    • National Cancer Center - Clinical Trial Pharmacy
    • Goyang-si Gyeonggi-do 10408 Korea, Republic of
    • National Cancer Center Urology center for Prostate Cancer
    • Goyang-si Gyeonggi-do 10408 Korea, Republic of
    • Seoul National University Bundang Hospital, Clinical Pharmacy
    • Seongnam-si Gyeonggido 13620 Korea, Republic of
    • Seoul National University Bundang Hospital
    • Seongnam-si Gyeonggido 13620 Korea, Republic of
    • Chungnam National University Hospital, Clinical Pharmacy
    • Daejeon 35015 Korea, Republic of
    • Chungnam National University Hospital
    • Daejeon 35015 Korea, Republic of
    • Severance Hospital Yonsei University Health System
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center - Clinical Trial Pharmacy
    • Seoul 05505 Korea, Republic of
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center Clinical Trial Pharmacy
    • Seoul 06351 Korea, Republic of
    • Samsung Medical Center
    • Seoul 06351 Korea, Republic of
    • Instituto Nacional de Cancerologia
    • Mexico Ciudad DE Mexico 14080 Mexico
    • Phylasis Clinicas Research S. de R.L. de C.V.
    • Cuautitlan Izcalli Estado DE Mexico 54769 Mexico
    • Centro de Investigación Clínica de Leon S.C.
    • Leon Guanajuato 37520 Mexico
    • Hospital Médica Campestre (Administradora Hospitalaria S.A de C.V.)
    • León Guanajuato 37180 Mexico
    • Rijnstate Arnhem
    • Arnhem 6815 AD Netherlands
    • Ziekenhuis Rijnstate
    • Arnhem 6815 AD Netherlands
    • St Apotheek der Haarlemse Ziekenhuizen
    • Haarlem 2035 RC Netherlands
    • Spaarne Gasthuis
    • Hoofddorp 2134 TM Netherlands
    • Maastricht University Medical Center
    • Maastricht 6229 HX Netherlands
    • Radboud University Medical Center
    • Nijmegen 6525 GA Netherlands
    • Radboudumc
    • Nijmegen 6525 GA Netherlands
    • Auckland City Hospital Pharmacy
    • Grafton Auckland 1023 New Zealand
    • Auckland City Hospital
    • Grafton Auckland 1142 New Zealand
    • Christchurch Hospital
    • Christchurch 8140 New Zealand
    • Waikato Hospital
    • Hamilton 3240 New Zealand
    • Akershus universitetssykehus HF
    • Lorenskog 1478 Norway
    • Akershus University Hospital
    • Lorenskog 1478 Norway
    • Sykehusapoteket Lorenskog
    • Nordbyhagen 1474 Norway
    • Avdeling for radiologi
    • Stavanger 4011 Norway
    • Sjukehusapoteket i Stavanger
    • Stavanger 4011 Norway
    • Stavanger University Hospital
    • Stavanger 4011 Norway
    • Centralny Szpital Kliniczny MSWiA
    • Warszawa Masovian 02-507 Poland
    • Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli
    • Lublin 20-090 Poland
    • Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE
    • Coimbra 3000-075 Portugal
    • IMACENTRO - Clínica de Imagiologia Médica do Centro, SA
    • Coimbra 3020-479 Portugal
    • Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos
    • Lisboa 1169-050 Portugal
    • Hospital CUF Descobertas, SA
    • Lisboa 1998-018 Portugal
    • Dr. Campos Costa - Consultório de Tomografia Computorizada, S.A.
    • Porto 4050-075 Portugal
    • Dr. Campos Costa - Consultório de Tomografia Computorizada, S.A.
    • Porto 4050-075 Portugal
    • Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António
    • Porto 4099-001 Portugal
    • Instituto Português de Oncologia do Porto Francisco Gentil, EPE
    • Porto 4200-072 Portugal
    • Centro Hospitalar de São João, EPE
    • Porto 4200-319 Portugal
    • "Sfantul Nectarie" Oncology Center
    • Craiova 200347 Romania
    • Republican Clinical Oncology Disp. of the MoH of Bashk. Rep.
    • Ufa Bashkortostan Republic 450054 Russian Federation
    • Private Medical Institution "Evromedservice"
    • Pushkin Saint Petersburg 196603 Russian Federation
    • University Clinic of Headaches, LLC
    • Moscow 109028 Russian Federation
    • University Clinic of Headaches, LLC
    • Moscow 121467 Russian Federation
    • MedScan RF clinic
    • Moscow 125565 Russian Federation
    • Research Institute of emergency n.a. Sklifosovskiy
    • Moscow 129090 Russian Federation
    • BHI of Omsk region "Clinical oncological dispensary"
    • Omsk 644013 Russian Federation
    • FGBIH "Clinical Hospital #122 n.a. L.G. Sokolov of Federal Medico-biological agency"
    • St. Petersburg 194291 Russian Federation
    • Non-State Healthcare Institution "Railway Clinical Hospital JSC RZhD"
    • St. Petersburg 195271 Russian Federation
    • First St. Petersburg State Medical University n.a. acad. I.P.Pavlov
    • St. Petersburg 197022 Russian Federation
    • FSBEI HE "First St. Petersburg State Medical University n.a. academician I.P Pavlov" MoH RF
    • St. Petersburg 197022 Russian Federation
    • FSBEI HE "First St. Petersburg State Medical University n.a. academician I.P Pavlov"
    • St. Petersburg 197022 Russian Federation
    • "Ramsay Diagnostics Rus", LLC
    • St. Petersburg 197046 Russian Federation
    • FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov
    • St. Petersburg 197758 Russian Federation
    • Hospital Orkli, LLC
    • St. Petersburg 199178 Russian Federation
    • Mart, Llc
    • St. Petersburg 199178 Russian Federation
    • Clinicodiagnostic center "MedExpert", LLC (CT)
    • Yaroslavl 150014 Russian Federation
    • SHI YR "Regional Clinical Oncology Hospital"
    • Yaroslavl 150054 Russian Federation
    • Institute for Oncology and Radiology of Serbia
    • Belgrade 11000 Serbia
    • Clinical Centre Nis, Clinic of Oncology
    • Nis 18000 Serbia
    • C.H. Univ. Santiago de Compostela
    • Santiago de Compostela A Coruña 15706 Spain
    • Complejo Hospitalario Universitario de Santiago
    • Santiago de Compostela A Coruña 15706 Spain
    • Hospital Comarcal General de Elda de Virgen de la Salud
    • Elda Alicante 03600 Spain
    • Hospital Universitario San Juan de Alicante
    • Sant Joan d'Alacant Alicante 03550 Spain
    • Hospital Universitario Central de Asturias
    • Oviedo Asturias 33011 Spain
    • Hospital Universitario Germans Trias i Pujol
    • Badalona Barcelona 08916 Spain
    • Institut Catalá d'Oncología - Hospital Duran i Reynals
    • l´Hospitalet de LLobregat Barcelona 08908 Spain
    • Institut Catalá d'Oncología
    • L´Hospitalet de Llobregat Barcelona 08908 Spain
    • Althaia. Xarxa Assistencial Universitaria de Manresa
    • Manresa Barcelona 08243 Spain
    • Corporacio Sanitaria Parc Tauli
    • Sabadell Barcelona 08208 Spain
    • Hospital Vithas Internacional Medimar
    • Alicante Comunidad Valenciana 03016 Spain
    • Hospital General Universitario de Elche
    • Elche Comunidad Valenciana 03203 Spain
    • Hospital Clinico Universitario de Valencia
    • Valencia Comunidad Valenciana 46010 Spain
    • C.H. Universitario de Vigo- Hospital Meixoeiro
    • Vigo Galicia 36200 Spain
    • C. H. Universitario de Vigo- Hospital Álvaro Cunqueiro
    • Vigo Galicia 36312 Spain
    • C. H. Universitario de Vigo-Hospital Alvaro Cunqueiro
    • Vigo Galicia 36312 Spain
    • Hospital Universitario Infanta Sofia
    • San Sebastian de los Reyes Madrid 28702 Spain
    • Hospital Universitario Infanta Sofia
    • San Sebastián de los Reyes Madrid 28702 Spain
    • Clinica Universidad de Navarra
    • Pamplona Navarra 31008 Spain
    • Complejo Hospitalario de Navarra
    • Pamplona Navarra 31008 Spain
    • Hospital HM Modelo
    • A Coruña 15011 Spain
    • Hospital Infanta Cristina
    • Badajoz 06080 Spain
    • Hospital del Mar
    • Barcelona 08003 Spain
    • Hospital Quiron of Barcelona
    • Barcelona 08023 Spain
    • Hospital Quirón de Barcelona
    • Barcelona 08023 Spain
    • Institut de Diagnòstic per la Imatge
    • Barcelona 08023 Spain
    • Hospital de La Santa Creu i Sant pau_Oncology department
    • Barcelona 08025 Spain
    • Hospital de La Santa Creu i Sant Pau
    • Barcelona 08025 Spain
    • CETIR Grup Medic
    • Barcelona 08029 Spain
    • Cetir, Centre Mèdic, S.L
    • Barcelona 08029 Spain
    • Hospital Universitario Vall d'Hebron
    • Barcelona 08035 Spain
    • Hospital Clinic de Barcelona
    • Barcelona 08036 Spain
    • Laboratorio Dr. F. Echevarne Analisis, S.A
    • Barcelona 08037 Spain
    • Hospital Provincial
    • Cordoba 14004 Spain
    • Hospital Universitario Reina Sofía
    • Cordoba 14004 Spain
    • Hospital Universitari de Girona Dr Josep Trueta. Institut Catala d'Oncologia.
    • Gerona 17007 Spain
    • Hospital Universitari de Girona Dr Josep Trueta.
    • Gerona 17007 Spain
    • Hospital Universitario Lucus Augusti
    • Lugo 27003 Spain
    • Fundacion Maria Rafols para la investigacion del Diagnostico de la imagen
    • Madrid 28006 Spain
    • Gabinete Radiologico Doctor Pita
    • Madrid 28006 Spain
    • Hospital General Universitario Gregorio Marañon
    • Madrid 28007 Spain
    • Hospital Universitario Infanta Leonor
    • Madrid 28031 Spain
    • Hospital Ruber Internacional
    • Madrid 28034 Spain
    • Hospital Ruber International
    • Madrid 28034 Spain
    • Hospital Universitario Ramon y Cajal_Oncology department
    • Madrid 28034 Spain
    • Hospital Universitario Ramon y Cajal
    • Madrid 28034 Spain
    • Hospital Clinico San Carlos
    • Madrid 28040 Spain
    • Hospital Universitario 12 de Octubre
    • Madrid 28041 Spain
    • Hospital Universitario La Paz
    • Madrid 28046 Spain
    • Hospital Universitario HM Sanchinarro - CIOCC
    • Madrid 28050 Spain
    • Hospital Universitario Virgen del Rocio
    • Sevilla 41013 Spain
    • Fundacion Instituto Valenciano de Oncologia
    • Valencia 46009 Spain
    • APL
    • Stockholm 171 64 Sweden
    • Karolinska University Hospital
    • Stockholm 171 76 Sweden
    • ApoEx VN
    • Örebro 701 85 Sweden
    • Örebro University Hospital
    • Örebro 701 85 Sweden
    • Clinical Trial Pharmacy, China Medical University Hospital
    • Taichung 40447 Taiwan
    • China Medical University Hospital
    • Taichung 404 Taiwan
    • Clinical Trial Pharmacy, Taichung Veterans General Hospital
    • Taichung 407 Taiwan
    • Taichung Veterans General Hospital
    • Taichung 407 Taiwan
    • Department of Pharmacy, National Cheng Kung University Hospital
    • Tainan 704 Taiwan
    • National Cheng Kung University Hospital
    • Tainan 704 Taiwan
    • Investigational Drug services, National Taiwan University Hospital
    • Taipei 100 Taiwan
    • Koo Foundation Sun Yat-Sen Cancer Center
    • Taipei 112 Taiwan
    • Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center
    • Taipei 112 Taiwan
    • National Taiwan University Hospital
    • Taipei Taiwan
    • Chang Gung Memorial Hospital, Linkou
    • Taoyuan 333 Taiwan
    • Chemotherapy pharmacy, Chang Gung Memorial Hospital, Linkou
    • Taoyuan 333 Taiwan
    • Churchill Hosptial
    • Headington Oxford OX3 7LJ United Kingdom
    • Royal United Hospitals Bath NHS Foundation Trust
    • Bath BA1 3NG United Kingdom
    • St Bartholomew 's Hospital, Barts Health NHS Trust
    • London EC1A 7BE United Kingdom
    • St. Bartholomew's Hospital, Barts Health NHS Trust
    • London EC1A 7BE United Kingdom
    • Guy's & St. Thomas' NHS Foundation Trust
    • London SE1 9RT United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital
    • London SE1 9RT United Kingdom
    • Clinical Trials Aseptic Unit (CTASU) Churchill Hospital
    • Oxford, Oxfordshire OX3 7LE United Kingdom
    • Churchill Hospital, Oxford University Hospitals NHS Trust
    • Oxford OX3 7LE United Kingdom

    View trial on ClinicalTrials.gov


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    Published June 5, 2017
  • A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer

    {{header-clinical-trials-navigation}}

    A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer


    Condition: Urothelial Cancer

    Intervention:

    • Biological: nivolumab
    • Biological: ipilimumab
    • Drug: gemcitabine
    • Drug: cisplatin
    • Drug: carboplatin

    Purpose: The purpose of this study is to determine whether an investigational immunotherapy nivolumab in combination with ipilimumab or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating patients with previously untreated inoperable or metastatic urothelial cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03036098

    Sponsor: Bristol-Myers Squibb

    Primary Outcome Measures:

    • Measure: Overall survival (OS) in cisplatin-ineligible randomized participants
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: OS in PD-L1 positive (>=1%) randomized participants by immunohistochemistry (IHC)
    • Time Frame: Up to 52 months
    • Safety Issue:
    • Measure: PFS by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in cisplatin-eligible participants with previously untreated, unresectable or metastatic Urothelial Carcinoma( UC)
    • Time Frame: Up to 55 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall survival (OS) in all randomized participants
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: PFS by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in cisplatin-ineligible randomized participants, in PD-L1 positive (≥1%) randomized participants and in all randomized participants
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Global Health Status score in all randomized participants
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: OS in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC.
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: European Organisation for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: PFS in PD-L1 positive by BICR (using RECIST 1.1)
    • Time Frame: Up to 55 months
    • Safety Issue:
    • Measure: OS by PD-L1 expression at ≥ 1% expression by immunohistochemistry (IHC)
    • Time Frame: Up to 55 months
    • Safety Issue:

    Estimated Enrollment: 990

    Study Start Date: March 24, 2017

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Metastatic or inoperable urothelial cancer
    • Must have at least 1 lesion with measurable disease
    • Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work
    • No prior systemic chemotherapy treatment in the metastatic setting Exclusion Criteria:
    • Patients with disease that is suitable for local therapy administered with curative intent
    • Patients with active brain metastases or leptomeningeal metastases
    • Patients with active, known or suspected autoimmune disease
    • Prior treatment with an anti-PD1, anti-PDL1, anti-PDL2, anti-CD137, or anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol defined inclusion/

    Exclusion Criteria:

    • Patients with disease that is suitable for local therapy administered with curative intent
    • Patients with active brain metastases or leptomeningeal metastases
    • Patients with active, known or suspected autoimmune disease
    • Prior treatment with an anti-PD1, anti-PDL1, anti-PDL2, anti-CD137, or anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol defined inclusion/exclusion criteria could apply

    Contact:

    • Recruiting sites have contact information. Please contact the sites directly. If there is no contact information,
    • please email:

    Locations:

    • Local Institution
    • Birmingham Alabama 35223 United States
    • Local Institution
    • Birmingham Alabama 35233 United States
    • Alaska Urological Institute dba Alaska Clinical Research Center
    • Anchorage Alaska 99503 United States
    • Local Institution
    • Little Rock Arkansas 72205 United States
    • VA of Central California Health Care System
    • Fresno California 93703 United States
    • St Joseph Heritage Healthcare
    • Santa Rosa California 95403 United States
    • Boca Raton Regional Hospital
    • Boca Raton Florida 33486 United States
    • Holy Cross Hospital
    • Fort Lauderdale Florida 33308 United States
    • Cancer Specialists of North FL
    • Jacksonville Florida 32207 United States
    • University Cancer Blood Ctr
    • Athens Georgia 30607 United States
    • Lewis Hall Singletary Oncology Center at John D. Archbold Memorial Hospital
    • Thomasville Georgia 31792 United States
    • University Of Illinois At Chicago
    • Chicago Illinois 60612 United States
    • Local Institution
    • Iowa City Iowa 55242 United States
    • Ochsner Clinic
    • New Orleans Louisiana 70121 United States
    • Beth Israel Deaconess Med Ctr
    • Boston Massachusetts 02215 United States
    • Dana Farber Cancer Institute
    • Boston Massachusetts 02215 United States
    • Milford Regional Medical Center
    • Boston Massachusetts 02215 United States
    • South Shore Hospital Cancer Center
    • Boston Massachusetts 02215 United States
    • St. Joseph Mercy Hospital
    • Ypsilanti Michigan 48197 United States
    • Ridges Cancer Clinic
    • Burnsville Minnesota 55337 United States
    • Hattiesburg Clinic
    • Hattiesburg Mississippi 39401 United States
    • St Lukes Hospital
    • Kansas City Missouri 64111 United States
    • Washington University School OF Medicine-Siteman Cancer Center
    • Saint Louis Missouri 63110 United States
    • GU Research Network, LLC
    • Omaha Nebraska 68130 United States
    • NH Oncology-Hematology, PA
    • Hooksett New Hampshire 03106 United States
    • University Of New Mexico
    • Albuquerque New Mexico 87131 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • NYU Winthrop Hospital Dept of Oncology/Hematology
    • Mineola New York 11501 United States
    • Icahn School Of Medicine At Mount Sinai
    • New York New York 10029 United States
    • Local Institution
    • New York New York 10065 United States
    • Duke University Medical Center
    • Durham North Carolina 27710 United States
    • The Ohio State University
    • Columbus Ohio 43210 United States
    • Providence Portland Med Ctr
    • Portland Oregon 97213 United States
    • Allegheny General Hospital
    • Pittsburgh Pennsylvania 15212 United States
    • Local Institution
    • Houston Texas 77030 United States
    • Local Institution
    • Salt Lake City Utah 84112 United States
    • Seattle Cancer Care Alliance
    • Kirkland Washington 98034 United States
    • Local Institution
    • Milwaukee Wisconsin 53226 United States
    • Instituto Medico Especializado Alexander Fleming
    • Capital Federal Buenos Aires 1426 Argentina
    • Hospital Privado De Comunidad
    • Mar Del Plata Buenos Aires 7600 Argentina
    • Clinica Viedma S.A.
    • Viedma RIO Negro 8500 Argentina
    • Centro De Diagnostico Urologico S.R.L.
    • Buenos Aires 1120 Argentina
    • Instituto Oncologico De Cordoba
    • Cordoba 5000 Argentina
    • Clinica Privada Universitaria Reina Fabiola
    • Cordoba 5004 Argentina
    • Local Institution
    • Darlinghurst New South Wales 2010 Australia
    • Local Institution
    • Waratah New South Wales 2298 Australia
    • Local Institution
    • Westmead New South Wales 2145 Australia
    • Local Institution
    • South Brisbane Queensland 4101 Australia
    • Local Institution
    • Tugan Queensland 4224 Australia
    • Local Institution
    • Heidelberg Victoria 3084 Australia
    • Local Institution
    • Nedlands Western Australia 6009 Australia
    • Hospital Sirio Libanes
    • Brasilia Distrito Federal 70200-730 Brazil
    • Associacao Hospital de Caridade Ijui
    • Ijui RIO Grande DO SUL 98700-000 Brazil
    • Hospital Sao Vicente De Paulo
    • Passo Fundo RIO Grande DO SUL 99010-080 Brazil
    • Hospital Sao Lucas Da Pucrs
    • Porto Alegre RIO Grande DO SUL 90610-000 Brazil
    • Centro de Pesquisas Oncologicas de Santa Catarina-CEPON
    • Florianopolis Santa Catarina 88034-000 Brazil
    • Fundacao Pio Xii Hosp Cancer De Barretos
    • Barretos SAO Paulo 14784-400 Brazil
    • Hospital De Base Da Faculdade De Medicina De Rio Preto
    • Sao Jose Do Rio Preto SAO Paulo 15090-000 Brazil
    • Local Institution
    • Sao Paulo 01509-900 Brazil
    • Nova Scotia Health Authority QEII Health Sciences Centre
    • Halifax Nova Scotia B3H 2Y9 Canada
    • London Regional Cancer Program, London Health Sciences Centre
    • London Ontario N6A 4L6 Canada
    • Centre integre universitaire de sante et de service sociaux de l'estrie - CHUS
    • Sherbrooke Quebec J1H 5N4 Canada
    • CHU de Quebec - L'Hotel-Dieu de Quebec
    • Quebec G1R 2J6 Canada
    • Local Institution
    • Santiago Metropolitana Chile
    • Centro Internacional de Estudios Clinicos
    • Recoleta Santiago DE Chile Chile
    • Oncocentro Apys
    • Vina del Mar Valparaiso 2520598 Chile
    • Local Institution
    • Vitacura Chile
    • Local Institution
    • Beijing Beijing 100001 China
    • Local Institution
    • Beijing Beijing 100034 China
    • Local Institution
    • Chongqing Chongqing 400030 China
    • Local Institution
    • Wuhan Hubei 430030 China
    • Local Institution
    • Nanjing Jiangsu 210000 China
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    • Nanjing Jiangsu 210008 China
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    • Nanjng Jiangsu China
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    • Hangzhou Zhejiang 310014 China
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    • Beijing 100083 China
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    • Hangzhou 310022 China
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    • Shanghai 200032 China
    • Klinika komplexni onkologicke pece
    • Brno 656 53 Czechia
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    • Hradec Kralove 500 05 Czechia
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    • Aalborg 9100 Denmark
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    • Herlev 2730 Denmark
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    • Helsinki 00029 Finland
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    • Lille 59000 France
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    • Marseille Cedex 9 13273 France
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    • Nimes Cedex 09 30029 France
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    • Saint Priest En Jarez 42271 France
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    • Suresnes 92151 France
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    • Tours Cedex 37044 France
    • Local Institution
    • Villejuif 94805 France
    • Universitat Dresden
    • Dresden 01307 Germany
    • Universitaetsklinikum Essen
    • Essen 45147 Germany
    • Medizinische Universitaetsklinik Freiburg
    • Freiburg 79106 Germany
    • Asklepios Klinik Altona
    • Hamburg 22763 Germany
    • Medizinische Hochschule Hannover
    • Hannover 30625 Germany
    • Universitaetsklinikum Jena
    • Jena 07747 Germany
    • Universitaetsklinikum Mannheim
    • Mannheim 68167 Germany
    • Local Institution
    • Muenchen 81675 Germany
    • Klinikum Nuernberg Nord, Urologische Klinik
    • Nuernberg 90419 Germany
    • Uniklinik Tuebingen
    • Tuebingen 72076 Germany
    • Kliniken Nordoberpfalz AG
    • Weiden 92637 Germany
    • Univ. Klinikum Wuerzburg
    • Wuerzburg 97080 Germany
    • Alexandra General Hospital
    • Athens 11528 Greece
    • Ioannina University Hospital
    • Ioannina 45500 Greece
    • Local Institution
    • Budapest 1122 Hungary
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    • Budapest 1145 Hungary
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    • Debrecen Hungary
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    • Miskolc 3526 Hungary
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    • Kfar Saba 44281 Israel
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    • Ramat Gan 52621 Israel
    • Ospedale S. Donato - Usl 8
    • Arezzo 52100 Italy
    • Ospedale Per Gli Infermi
    • Faenza 48018 Italy
    • IRST Meldola
    • Forli 47014 Italy
    • Ospedale Della Misericordia Grosseto
    • Grosseto 58100 Italy
    • IRCCS Istituto Nazionale Tumori Milano
    • Milano 20133 Italy
    • Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli
    • Napoli 80131 Italy
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    • Hirosaki-shi Aomori 036-8563 Japan
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    • Chiba-shi Chiba 260-8717 Japan
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    • Matsuyama-shi Ehime 7910280 Japan
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    • Fukuoka-shi Fukuoka 8128582 Japan
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    • Sapporo-city Hokkaido 0608543 Japan
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    • Tsukuba-shi Ibaraki 3058576 Japan
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    • Morioka-shi Iwate 0208505 Japan
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    • Kita-Gun Kagawa 7610793 Japan
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    • Niigata-shi Niigata 9518520 Japan
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    • Osakasayama Osaka 589-8511 Japan
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    • Hamamatsu-shi Shizuoka 431-3192 Japan
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    • Ube City Yamaguchi 755-8505 Japan
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    • Seongnam-si 13620 Korea, Republic of
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    • Seoul 03080 Korea, Republic of
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    • Seoul 03722 Korea, Republic of
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    • Seoul 05505 Korea, Republic of
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    • Monterrey Nuevo LEON 64460 Mexico
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    • Amsterdam 1066 CX Netherlands
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    • Enschede 7512KZ Netherlands
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    • Groningen 9713 GZ Netherlands
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    • Leeuwarden 8934 AD Netherlands
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    • Bergen 5021 Norway
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    • Lorenskog 1478 Norway
    • Instituto Nacional De Enfermedades Neoplasicas
    • Lima 34 Peru
    • Clinica El Golf
    • Lima Lima 27 Peru
    • Ambulatorium Chemioterapii
    • Bydgoszcz 85-796 Poland
    • Oddzial Dzienny Chemioterapii
    • Koszalin 75-581 Poland
    • Klinika Nowotworow Ukladu Moczowego Centrum Onkologii - Inst
    • Warszawa 02-781 Poland
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    • Cluj-Napoca 400015 Romania
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    • Craiova 200347 Romania
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    • Moscow 115478 Russian Federation
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    • Moscow 117997 Russian Federation
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    • Moscow 125367 Russian Federation
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    • Novosibirsk 630099 Russian Federation
    • Local Institution
    • St Petersburg 198255 Russian Federation
    • Local Institution
    • Singapore 169610 Singapore
    • Comp. Hosp. Univ. A Coruna
    • A Coruna 15006 Spain
    • Hospital Santa Creu I Sant Pau
    • Barcelona 08025 Spain
    • Hospital Universitario Ramon Y Cajal
    • Madrid 28034 Spain
    • Hosp Univer 12 De Octubre
    • Madrid 28041 Spain
    • H. U. Marques de Valdecilla
    • Santander 39008 Spain
    • Hosp. Univ. Virgen Del Rocio
    • Sevilla 41013 Spain
    • Instituto Valenciano De Oncologia
    • Valencia 46009 Spain
    • Local Institution
    • Jonkoping 551 85 Sweden
    • Local Institution
    • Linkoping 581 85 Sweden
    • Local Institution
    • Lund 221 85 Sweden
    • Kantonsspital Baden
    • Baden 5404 Switzerland
    • Kantonsspital Graubuenden
    • Chur 7000 Switzerland
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    • Kaohsiung 883 Taiwan
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    • Taichung 40705 Taiwan
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    • Taipei 100 Taiwan
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    • Taipei 11217 Taiwan
    • Local Institution
    • Taoyuan 333 Taiwan
    • Local Institution
    • Ankara 06590 Turkey
    • Local Institution
    • Istanbul 34300 Turkey
    • Local Institution
    • Izmir 35340 Turkey

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published January 18, 2018
  • A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therap

    {{header-clinical-trials-navigation}}

    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therapy


    Condition: Urothelial Carcinoma

    Intervention:

    • Drug: Ramucirumab
    • Drug: Docetaxel
    • Drug: Placebo

    Purpose: The main purpose of this study is to evaluate the safety and efficacy of the study drug ramucirumab in combination with docetaxel in participants with urothelial cancer who failed prior platinum-based therapy.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02426125

    Sponsor: Eli Lilly and Company

    Primary Outcome Measures:

    • Measure: Progression Free Survival
    • Time Frame: Randomization to Radiological Disease Progression or Death from Any Cause (Approximately 19 Months)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall Survival
    • Time Frame: Randomization to Date of Death from Any Cause (Approximately 33 Months)
    • Safety Issue:
    • Measure: Objective Response Rate (ORR)
    • Time Frame: Randomization to Disease Progression (Approximately 33 Months)
    • Safety Issue:
    • Measure: Disease Control Rate
    • Time Frame: Randomization to Disease Progression (Approximately 33 Months)
    • Safety Issue:
    • Measure: Duration of Response (DoR)
    • Time Frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 33 Months)
    • Safety Issue:
    • Measure: Change from Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
    • Time Frame: Randomization, 30 Days After Treatment Discontinuation (Approximately 33 Months)
    • Safety Issue:
    • Measure: Change from Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)
    • Time Frame: Randomization, 30 Days After Treatment Discontinuation (Approximately 33 Months)
    • Safety Issue:
    • Measure: Pharmacokinetics (PK): Minimum Concentration (CMIN) of Ramucirumab
    • Time Frame: Predose Cycle 1 through 30 Days After Treatment Discontinuation (Approximately 33 Months)
    • Safety Issue:
    • Measure: Number of Participants with Anti-Ramucirumab Antibodies
    • Time Frame: Predose Cycle 1 through 30 Days After Treatment Discontinuation (Approximately 33 Months)
    • Safety Issue:

    Estimated Enrollment: 466

    Study Start Date: July 2015

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Have histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis.
    • Had disease progression while on a platinum containing regimen in the first-line setting or within 14 months after completing the first-line platinum regimen. Participants who received treatment with one immune checkpoint inhibitor regimen are eligible (for example PD-1, PDL1, or CTLA4) and may have a longer interval since prior platinum-containing therapy (≤24 months).
    • Have a life expectancy of ≥3 months.
    • Have received no more than one prior systemic chemotherapy regimen in the relapsed or metastatic setting. Prior treatment with no more than one prior immune checkpoint inhibitor is permitted and will not be considered as a line of systemic chemotherapy.
    • Have measurable disease or nonmeasurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
    • Have an Eastern Cooperative Oncology Group (ECOG) of 0 or 1.
    • Have adequate hematologic function.
    • Have adequate coagulation function.
    • Have adequate hepatic function.
    • The participant does not have:
    • cirrhosis at a level of Child-Pugh B (or worse)
    • cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis
    • Have adequate renal function as defined by creatinine clearance >30 milliliters/minute.
    • Have urinary protein ≤1+ on dipstick or routine urinalysis.
    • The participant is willing to provide blood, urine, and tissue samples for research purposes.

    Exclusion Criteria:

    • Have received more than one prior systemic chemotherapy regimen for metastatic disease.
    • Have received prior systemic taxane therapy for transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic).
    • Have received more than one prior antiangiogenic agent (that is, bevacizumab, sorafenib, sunitinib) for TCC of the urothelium.
    • Have received radiation therapy within 4 weeks (≤4 weeks) prior to randomization or has not recovered from toxic effects of the treatment that was given >4 weeks prior to randomization.
    • Have a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
    • Have experienced a Grade ≥3 bleeding event within 3 months (≤3 months) prior to randomization.
    • Have uncontrolled intercurrent illness, including, but not limited to symptomatic anemia, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness, or any other serious uncontrolled medical disorders.
    • Have experienced any arterial or venothrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 6 months (≤6 months) prior to randomization.
    • Have known untreated brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease.
    • Have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related illness.
    • Have undergone major surgery within 28 days (≤28 days) prior to randomization or subcutaneous venous access device placement within 7 days (≤7 days) prior to randomization.
    • The participant is pregnant prior to randomization or lactating.
    • Have a concurrent malignancy or had another malignancy within 5 years (≤5 years) of study enrollment.

    Locations:

    • Highlands Oncology Group
    • Fayetteville Arkansas 72703 United States
    • St. Jude Medical Center
    • Fullerton California 92835 United States
    • UCLA Medical Center
    • Los Angeles California 90024 United States
    • USC Norris Cancer Hospital
    • Los Angeles California 90033 United States
    • SMO TRIO -Translational Research
    • Los Angeles California 90095 United States
    • Cancer Care Associates Medical Group
    • Redondo Beach California 90277 United States
    • University of California, Davis - Health Systems
    • Sacramento California 95817 United States
    • Central Coast Medical Oncology Corporation
    • Santa Monica California 93454 United States
    • University of Colorado
    • Aurora Colorado 80045 United States
    • Pharmatech Oncology Inc
    • Denver Colorado 80203 United States
    • St Mary's Hospital Regional Cancer Center
    • Grand Junction Colorado 81501 United States
    • Yale University School of Medicine
    • New Haven Connecticut 06520 United States
    • Southeast Florida Hematology/Oncology
    • Fort Lauderdale Florida 33308 United States
    • Florida Cancer Specialists
    • Fort Myers Florida 33916 United States
    • Lakeland Regional Cancer Center
    • Lakeland Florida 33805 United States
    • Sylvester Comprehensive Cancer Center
    • Miami Florida 33136 United States
    • Florida Cancer Specialists
    • Saint Petersburg Florida 33705 United States
    • Southeastern Regional Medical Center
    • Newnan Georgia 30265 United States
    • The Queen's Medical Center
    • Honolulu Hawaii 96813 United States
    • Fort Wayne Oncology & Hematology
    • Fort Wayne Indiana 46845 United States
    • Alton Ochsner Medical Center
    • New Orleans Louisiana 70121 United States
    • University of Maryland- Biological Sciences
    • Baltimore Maryland 21201 United States
    • Karmanos Cancer Institute
    • Detroit Michigan 48201 United States
    • Mayo Clinic
    • Rochester Minnesota 55902 United States
    • University of Nebraska Medical Center
    • Omaha Nebraska 68198-7680 United States
    • Cornell University Medical College
    • New York New York 10021 United States
    • SUNY at Stony Brook
    • Stony Brook New York 11794 United States
    • Oncology Hematology Care Inc.
    • Cincinnati Ohio 45242 United States
    • University of Oklahoma Health Sciences Center
    • Oklahoma City Oklahoma 73104 United States
    • SMO Sarah Cannon Research Inst.
    • Nashville Tennessee 37203 United States
    • The Center for Cancer and Blood Disorders
    • Fort Worth Texas 76104 United States
    • Inova Comprehensive Cancer Care & Research Institute
    • Fairfax Virginia 22031 United States
    • University of Washington Medical Center
    • Seattle Washington 98109 United States
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Adelaide 5000 Australia
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    • Footscray 3011 Australia
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    • Randwick 2031 Australia
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    • Subiaco 6008 Australia
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    • Brussels 1200 Belgium
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    • Leuven 3000 Belgium
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    • Wilrijk 2610 Belgium
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    • Toronto M4N 3M5 Canada
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    • Vancouver V5Z 4E6 Canada
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    • Herlev 2730 Denmark
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    • Odense 5000 Denmark
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    • Caen 14076 France
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    • Lille 59020 France
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    • Lyon 69373 France
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    • Montpellier 34070 France
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    • Paris 75015 France
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    • Rennes 35062 France
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    • Dusseldorf 40225 Germany
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    • Freiburg 79106 Germany
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    • Homburg 66421 Germany
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    • Jena 07740 Germany
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    • Marburg 35043 Germany
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    • Tubingen 72076 Germany
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    • Athens 11528 Greece
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    • Heraklion 71110 Greece
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    • Patras 26504 Greece
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    • Thessaloniki 56403 Greece
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Budapest 1122 Hungary
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    • Miskolc 3526 Hungary
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Haifa 3525408 Israel
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    • Kfar Saba 4428164 Israel
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    • Petach Tikva 4941492 Israel
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    • Tel Hashomer 5265601 Israel
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    • Tel-Aviv Jaffa 6423906 Israel
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    • Zerifin 6093000 Israel
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    • Arezzo 52100 Italy
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    • Bologna 40138 Italy
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    • Milano 20133 Italy
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    • Orbassano 10043 Italy
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    • Rome 00152 Italy
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    • Verona 37134 Italy
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    • Bunkyo-ku 113-8431 Japan
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    • Chiba 260-8717 Japan
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    • Fukuoka 812-8582 Japan
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    • Hidaka 350-1298 Japan
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    • Hirosaki 036-8563 Japan
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    • Kashiwa 277-8577 Japan
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    • Kita-gun 761-0793 Japan
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    • Kobe 650-0047 Japan
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    • Matsuyama 791-0280 Japan
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    • Morioka 020-8505 Japan
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    • Niigata 951-8520 Japan
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    • Osaka 541-8567 Japan
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    • Sapporo 060-8543 Japan
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    • Sendai 980-8574 Japan
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    • Suita-shi 565-0871 Japan
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    • Tokyo 135-8550 Japan
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    • Tsukuba 305-8576 Japan
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    • Daejeon 35015 Korea, Republic of
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    • Seongnam-si 13620 Korea, Republic of
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    • Seongnam 463-707 Korea, Republic of
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    • Seoul 03181 Korea, Republic of
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    • Seoul 03722 Korea, Republic of
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    • Seoul 05505 Korea, Republic of
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    • Seoul 06351 Korea, Republic of
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    • Aguascalientes 20230 Mexico
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    • Culiacan 80020 Mexico
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    • Mexico 06760 Mexico
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    • Monterrey 64570 Mexico
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    • Morelia 58260 Mexico
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    • Amsterdam 1066 CX Netherlands
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    • Arnhem 6815 AD Netherlands
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    • Maastricht 6229 HX Netherlands
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    • Rotterdam 3075 EA Netherlands
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    • Sittard 6162 BG Netherlands
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    • Gdansk 80-219 Poland
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    • Poznan 60-569 Poland
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    • Warszawa 04-125 Poland
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    • Wieliszew 05-135 Poland
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    • Baia Mare 430110 Romania
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    • Cluj-Napoca 400058 Romania
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    • Craiova 200347 Romania
    • Ivanovo regional clinical oncology dispensary
    • Ivanovo 153040 Russian Federation
    • Republic Oncology Dispensary of MoH of Republic Tatarstan
    • Kazan 420029 Russian Federation
    • Scientific research oncology institute n.a. P. A. Herzen
    • Moscow 125284 Russian Federation
    • Saint-Petersburg city clinical oncology dispensary
    • Saint Petersburg 198255 Russian Federation
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    • Saratov 410054 Russian Federation
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    • Badajoz 06080 Spain
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    • Barcelona 08907 Spain
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    • Madrid 28034 Spain
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    • Kaohsiung 83301 Taiwan
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    • Taichung 40705 Taiwan
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    • Tainan 71004 Taiwan
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    • Taipei 100 Taiwan
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    • Ankara 06100 Turkey
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    • Antalya 07059 Turkey
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    • Edirne 22030 Turkey
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    • Istanbul 34098 Turkey
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    • Malatya 44280 Turkey
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    • Dnipropetrovsk 49102 Ukraine
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    • Kyiv 04107 Ukraine
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    • Lutsk 63000 Ukraine
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    • Bebington CH63 4JY United Kingdom
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    • Chelsea W6 8RF United Kingdom
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    • London EC1A 7BE United Kingdom
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    • Nottingham NG5 1PB United Kingdom
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    • Southampton SO16 6YD United Kingdom
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    • Sutton SM2 5PT United Kingdom

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Select

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    A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications


    Condition: Solid Tumors

    Intervention:

    • Drug: Avelumab

    Purpose: This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in subjects with selected tumor indications. New recruitment is open for all active cohorts. Active cohorts: Escalation revised dosing regimen cohort. Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01772004

    Sponsor: EMD Serono

    Primary Outcome Measures:

    • Measure: Dose Limiting Toxicity
    • Time Frame: Up to 3 weeks
    • Safety Issue:
    • Measure: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) for Efficacy Expansion Cohorts
    • Time Frame: Every 6 weeks for first 12 months, then 12-weekly until end of treatment and post treatment every 3 months ( up to 52 months)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0
    • Time Frame: Screening up to 10 weeks after last treatment
    • Safety Issue:
    • Measure: Pharmacokinetic parameters: AUC (0-t), AUC (0-infinity), λz, Cmax, Tmax, T(1/2) of avelumab
    • Time Frame: Every 6-week up to Week 25
    • Safety Issue:
    • Measure: Immune-related Best Overall Response (irBOR) and Best Overall Response (BOR) according to modified Immune-related response criteria (irRC) and RECIST version 1.1, respectively
    • Time Frame: Time from inclusion in the trial until the date of first documented progression or discontinuation from the study due to any cause, up to 1 year after last treatment
    • Safety Issue:
    • Measure: Immune-related Progression-Free Survival (irPFS) time and Progression-Free Survival (PFS) Time according to modified irRC and RECIST version 1.1 , respectively
    • Time Frame: Time from inclusion in the trial until first observation of progressive disease or death when death occurs within 12 weeks of the last tumor assessment or first administration of trial treatment (whichever is later) up to 1 year after last treatment
    • Safety Issue:
    • Measure: Overall Survival Time
    • Time Frame: Time from randomization to death anticipated up to 2 years after last treatment
    • Safety Issue:
    • Measure: Pharmacodynamic profile of avelumab to include serum levels of cytokines
    • Time Frame: Up to Week 25
    • Safety Issue:
    • Measure: Number of subjects with anti-avelumab antibodies
    • Time Frame: Every 6-week up to Week 25
    • Safety Issue:
    • Measure: Level of PD-L1 tumor expression
    • Time Frame: Every 6-week up to Week 25
    • Safety Issue:
    • Measure: Unconfirmed response according to RECIST 1.1 per investigator assessment for Primary expansion cohort
    • Time Frame: Week 13
    • Safety Issue:
    • Measure: Duration of response according to modified irRC and RECIST 1.1 per investigator assessment
    • Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment
    • Safety Issue:
    • Measure: Progression Free Survival time according to RECIST 1.1 for Efficacy Expansion Cohorts
    • Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment
    • Safety Issue:
    • Measure: Duration of response according to RECIST 1.1 for Efficacy Expansion cohorts
    • Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment
    • Safety Issue:
    • Measure: Confirmed BOR as per RECIST 1.1 as adjudicated by an Independent Endpoint Review Committee (IERC) for secondary urothelial carcinoma cohort
    • Time Frame: Time Frame: Every 6 weeks for first 12 months, then 12-weekly until end of treatment and post treatment every 3 months ( up to 52 months)
    • Safety Issue:

    Estimated Enrollment: 1756

    Study Start Date: January 31, 2013

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • for dose escalation and expansion phase:
    • Signed written informed consent
    • Male or female subjects aged greater than or equal to 18 years
    • Subjects must have histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
    • Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST 1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease without a measureable lesion
    • Adequate hematological, hepatic and renal function as defined in the protocol
    • Effective contraception for both male and female subjects if the risk of conception exists
    • Other protocol defined inclusion criteria could apply Inclusion Criteria for expansion phase:
    • Subjects must have relapsed, refractory, or progressive disease following last line of treatment (with the exception of the gastric and gastroesophageal junction (GEJ) cancer cohort, which does not require progression). Availability of tumor archival material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen must have been collected within 90 days prior to the first investigational medicinal product (IMP) administration. Specifically, the following will be required:
    • NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or stage IV NSCLC that has progressed after 1 line of platinum-containing doublet chemotherapy. Subjects should have received only 1 line of platinum-containing treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing regimen is not sufficient for eligibility because not received in the context of a metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA
    • NSCLC first line: Stage IV (per 7th International Association for the Study of Lung Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven. Subjects must not have received treatment for their metastatic or recurrent disease. No activating epidermal growth factor receptor (EGFR) mutation nor ALK translocation/re-arrangement
    • Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with first-line chemotherapy combination with or without disease progression. Subjects should have received no more than 1 line of treatment for metastatic disease. Subjects should not have been treated with trastuzumab (but can be Human Epidermal growth factor Receptor 2 [HER2] positive). Subjects who received any platinum containing doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately candidates for surgery will also be eligible, as long as they did not have progressive disease after completion of the neoadjuvant chemotherapy. In addition, subjects with gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte count is as defined in the protocol
    • MBC: Subjects must have histologically confirmed locally advanced or MBC and have tumor that is refractory to or progressive after standard of care therapy. Subjects must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease. Subjects must have received a taxane and an anthracycline, unless contra-indicated
    • Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC, mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol
    • Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as defined in the protocol
    • Other protocol defined inclusion criteria for expansion phase could apply

    Exclusion Criteria:

    • for dose escalation and expansion phase:
    • Concurrent treatment with a non-permitted drug
    • Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
    • Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment; or concurrent systemic therapy with immunosuppressive agents, use of hormonal agents within 7 days before the start of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
    • Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
    • Rapidly progressive disease (for example, tumor lysis syndrome)
    • Active or history of central nervous system metastases
    • Receipt of any organ transplantation including allogeneic stem-cell transplantation
    • Significant acute or chronic infections as defined in the protocol
    • Active or history of any autoimmune disease (subjects with diabetes Type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies
    • Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
    • Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0, however sensory neuropathy less than or equal to Grade 2 is acceptable
    • Pregnancy or lactation period
    • Known alcohol or drug abuse
    • Clinically significant (that is, active) cardiovascular disease
    • All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment
    • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
    • Legal incapacity or limited legal capacity
    • Non-oncology vaccine therapies for prevention of infection disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine

    Contact:

    • US Medical Information
    • 888-275-7376

    Locations:

    • For Recruiting Locations in the United States, please Contact U.S. Medical Information
    • Rockland Massachusetts United States
    • Please contact the Merck KGaA Communication Center
    • Leuven Belgium
    • Please contact the Merck KGaA Communication Center
    • Praha Czechia
    • Please contact the Merck KGaA Communication Center
    • Paris France
    • Please contact the Merck KGaA Communication Center
    • Berlin Germany
    • Please contact the Merck KGaA Communication Center
    • Budapest Hungary
    • Please contact the Merck KGaA Communication Center
    • Seoul Korea, Republic of
    • Please contact the Merck KGaA Communication Center
    • Warszawa Poland
    • Please contact the Merck KGaA Communication Center
    • Taipei Taiwan
    • Please contact the Merck KGaA Communication Center
    • London United Kingdom

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • A Phase I/1b Study of Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

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    A Phase I/1b Study of Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer


    Condition: Bladder Cancer, Carcinoma, Transitional Cell, Renal Pelvis Cancer, Ureter Cancer, Urethra Cancer

    Intervention:

    • Drug: Enzalutamide
    • Drug: Cisplatin
    • Drug: Gemcitabine

    Purpose: The main purpose of this study is to find out the dose of enzalutamide that can be safely given with gemcitabine and cisplatin in patients with advanced bladder cancer. Researchers also want to find out the side effects of these drugs when given together. This study will also help in finding out the effect on tumor of the combination of enzalutamide, gemcitabine and cisplatin.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02300610

    Sponsor: H. Lee Moffitt Cancer Center and Research Institute

    Primary Outcome Measures:

    • Measure: Maximum Tolerated Dose (MTD)
    • Time Frame: Up to 6 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR)
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: Progression Free Survival (PFS)
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: Overall Survival (OS)
    • Time Frame: Up to 6 months
    • Safety Issue:

    Estimated Enrollment: 24

    Study Start Date: February 11, 2015

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Cytologically or histologically confirmed evidence of transitional cell carcinoma of bladder, renal pelvis, ureter or urethra.
    • Patients with Stage IV (locally advanced or metastatic) disease. Must have measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST).
    • Minimum of 4 weeks since any major surgery, completion of radiation.
    • Prior treatment with cytotoxic chemotherapy is not a requirement, but allowed only if used in neoadjuvant, adjuvant or for bladder preserving protocols, as long as was administered > 6 months prior to starting study.
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
    • Life expectancy 12 weeks or more.
    • Must have normal organ and marrow function.
    • Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating.
    • Sexually active women of childbearing age and men should be willing to follow birth control guidelines.
    • Should be able to swallow enzalutamide and comply with study requirements.

    Exclusion Criteria:

    • Prior treatment with any cytotoxic chemotherapy in metastatic setting. Prior treatment with cytotoxic chemotherapy is allowed only if used in neoadjuvant, adjuvant or for bladder preserving protocols, as long as was administered > 6 months prior to starting study.
    • Have undergone major surgery within 4 weeks prior to study enrollment.
    • Chronic treatment with steroids or any other immunosuppressant drugs.
    • Should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.
    • History of seizures, predisposing factors for seizures, including underlying brain injury with loss of consciousness within previous 12 months, transient ischemic attack within previous 12 months, cerebral vascular accident or brain arteriovenous malformation.
    • Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
    • Congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the 6 months preceding enrollment.
    • Known history of HIV.
    • Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
    • Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice birth control guidelines.
    • Concurrent medications which strongly inhibit or induce CYP enzymes (gemfibrozil, Rifampin, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin, St. John's Wort).
    • History of stage III or greater cancer, except basal or squamous cell skin cancers adequately treated or any other stage I or II cancer adequately treated and disease-free for ≥ 2 years. Incidental findings of stage I or II prostate cancer that is considered to be cured with radical cystoprostatectomy is allowed.
    • Prior use of enzalutamide.
    • Radiation therapy via external beam or brachytherapy within 28 days of registration.
    • Patients who are ineligible to receive cisplatin: Creatinine clearance of less than 60 mL/minute, hearing loss of 25 decibel (dB) at 2 contiguous frequencies, grade 2 or higher peripheral neuropathy, or New York Heart Association Class III or higher heart failure.
    • Allergy/sensitivity to any study drug (gemcitabine, cisplatin, enzalutamide), or drugs chemically related to study drug, or excipients.
    • Brain metastases (including treated or stable brain metastases)

    Locations:

    • H. Lee Moffitt Cancer Center and Research Institute
    • Tampa Florida 33612 United States
    • University of Minnesota, Masonic Cancer Center
    • Minneapolis Minnesota 55455 United States

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-7435) for Metastatic Urothelial Cancer Refractory to Platinum

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    A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-7435) for Metastatic Urothelial Cancer Refractory to Platinum


    Condition: Stage IV Bladder Urothelial Carcinoma

    Intervention:

    • Procedure: Computed Tomography
    • Other: Laboratory Biomarker Analysis
    • Biological: Pembrolizumab
    • Procedure: Positron Emission Tomography
    • Biological: Recombinant EphB4-HSA Fusion Protein

    Purpose: This phase II trial studies how well recombinant EphB4-HSA fusion protein and pembrolizumab work in treating patients with urothelial (bladder) cancer that has spread from the primary site to other places in the body or has come back and does not respond to certain chemotherapy drugs. Combinations of biological substances in recombinant EphB4-HSA fusion protein may be able to carry tumor-killing substances directly to urothelial cancer cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Giving recombinant EphB4-HSA fusion protein and pembrolizumab together may be a better treatment for patients with urothelial cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02717156

    Sponsor: University of Southern California

    Primary Outcome Measures:

    • Measure: Incidence of toxicities and adverse events classified according to the Common Terminology Criteria for Adverse Events v4.03
    • Time Frame: Up to 30 days
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: OR defined as complete response or partial response according to RECIST v 1.1
    • Time Frame: Up to 3 years
    • Safety Issue:

    Estimated Enrollment: 60

    Study Start Date: November 21, 2016

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Be willing and able to provide written informed consent/assent for the trial
    • Advanced (metastatic or recurrent) pathologically proven urothelial carcinoma which is refractory to platinum based due to disease progression on a platinum containing regimen; patients progressing within 12 months of their last dose of platinum-based neoadjuvant or adjuvant chemotherapy will be considered platinum refractory
    • Have measurable disease based on RECIST 1.1
    • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained for up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor; an optional core biopsy will be requested from an accessible metastatic site after 2 cycles of treatment
    • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
    • Absolute neutrophil count (ANC) >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
    • Measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN)
    • Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN or =< 5 X ULN for subjects with liver metastases
    • Albumin >= 2.5 mg/dL
    • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
    • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
    • Recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
    • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
    • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

    Exclusion Criteria:

    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
    • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
    • Has a known history of active TB (bacillus tuberculosis)
    • Hypersensitivity to pembrolizumab or any of its excipients
    • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
    • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
    • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin or early stage carcinoma of the cervix that has undergone potentially curative therapy or in situ cervical cancer; patients with incidental prostate cancer diagnosed at cystectomy or deemed appropriate for surveillance based on national guidelines will be allowed to enroll
    • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
    • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
    • Has known history of, or any evidence of active, non-infectious pneumonitis
    • Has an active infection requiring systemic therapy
    • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA
    • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
    • Has known active Hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
    • Major systemic infection requiring antibiotics 72 hours or less prior to first dose of study drug
    • Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or pembrolizumab (MK-3475) or places the patient at undue risk for treatment related complications
    • Any other condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
    • Any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis
    • Has received a live vaccine within 30 days of planned start of study therapy; Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, flu-mist) are live attenuated vaccines, and are not allowed

    Contact:

    • Cheryl Kefauver, RN
    • 323-865-0459

    Locations:

    • City of Hope
    • Duarte California 91010 United States
    • USC / Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab With or Without Platinum-Based Combination Chemotherapy Versus Chemotherapy in Subjects With Advanced or Metastatic Urothelial Carcinoma

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    A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab With or Without Platinum-Based Combination Chemotherapy Versus Chemotherapy in Subjects With Advanced or Metastatic Urothelial Carcinoma


    Condition: Urothelial Carcinoma Associated 1 RNA, Human

    Intervention:

    • Biological: Pembrolizumab
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Gemcitabine

    Purpose: The purpose of this study is to determine the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy versus chemotherapy alone in participants with advanced or metastatic urothelial carcinoma (bladder cancer). The primary hypotheses are that pembrolizumab plus chemotherapy is superior to chemotherapy alone with respect to Progression-free Survival (PFS) and Overall Survival (OS) in participants with programmed cell death ligand 1 (PD-L1) positive tumors (Combined Positive Score [CPS] ≥10%) and in all participants (includes those participants with PD-L1 positive tumors and those with PD-L1 negative tumors [CPS <10%]).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02853305

    Sponsor: Merck Sharp & Dohme Corp.

    Primary Outcome Measures:

    • Measure: Progression-free Survival (PFS) Using Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    • Time Frame: Up to approximately 24 months
    • Safety Issue:
    • Measure: Overall Survival (OS)
    • Time Frame: Up to approximately 24 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Number of Participants Who Experience an Adverse Event (AE)
    • Time Frame: Up to approximately 27 months
    • Safety Issue:
    • Measure: Number of Participants Who Discontinue Study Drug Due to an AE
    • Time Frame: Up to approximately 24 months
    • Safety Issue:
    • Measure: Objective Response Rate (ORR) Using RECIST 1.1 as Assessed by BICR
    • Time Frame: Up to approximately 24 months
    • Safety Issue:
    • Measure: Disease Control Rate (DCR) Using RECIST 1.1 as Assessed by BICR
    • Time Frame: Up to approximately 24 months
    • Safety Issue:
    • Measure: PFS Using RECIST 1.1 as Assessed by BICR at Milestone Timepoints
    • Time Frame: At 6, 12, 18 and 24 months
    • Safety Issue:
    • Measure: Duration of Response (DOR) Using RECIST 1.1 as Assessed by BICR
    • Time Frame: Up to approximately 24 months
    • Safety Issue:
    • Measure: Change from Baseline in Health-related Quality of Life Score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
    • Time Frame: Baseline and 24 months
    • Safety Issue:

    Estimated Enrollment: 990

    Study Start Date: September 15, 2016

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma of the renal pelvis, ureter [upper urinary tract], bladder, or urethra. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology.
    • Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
    • Has received no prior systemic chemotherapy for advanced or metastatic urothelial carcinoma, with the following exceptions:
    • Neoadjuvant platinum-based chemotherapy with recurrence >12 months from completion of therapy is permitted.
    • Adjuvant platinum-based chemotherapy following radical cystectomy with recurrence >12 months from completion of therapy is permitted.
    • Has provided tissue for biomarker analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated from a muscle invasive urothelial carcinoma or a metastatic biopsy, originally from the original tumor.
    • Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
    • Demonstrates adequate organ function.
    • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of pembrolizumab or 180 days after chemotherapy treatment.
    • Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab or 180 days after chemotherapy treatment.

    Exclusion Criteria:

    • Has disease that is suitable for local therapy administered with curative intent.
    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.
    • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
    • Has an active autoimmune disease that has required systemic treatment in the past 2 years.
    • Has had a prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to the first dose of study drug (6 weeks for nitrosoureas or mitomycin C) or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events (AEs) due to mAbs administered more than 4 weeks earlier.
    • Has not recovered (i.e., AE ≤ Grade 1 or at Baseline) from AEs due to a previously administered agent.
    • Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.
    • Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
    • A history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score ≤6; Prostate-specific Antigen (PSA) level undetectable.
    • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
    • Has a known history of active tuberculosis (TB).
    • Has an active infection requiring systemic therapy.
    • Has a history of severe hypersensitivity reaction (e.g. generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to pembrolizumab, gemcitabine, carboplatin, or cisplatin or their analogs and/or to any of their excipients.
    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is a known regular user (including "recreational use") of any illicit drug(s) or had a recent history (within the last year) of drug or alcohol abuse.
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapy treatment.
    • Has received prior therapy with an anti-PD-1, or anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137).
    • Has a known history of human immunodeficiency virus (HIV).
    • Has known active hepatitis B or hepatitis C.

    Contact:

    • Toll Free Number
    • 1-888-577-8839

    Locations:

    • Call for Information (Investigational Site 3575)
    • Chandler Arizona 85224 United States
    • Call for Information (Investigational Site 8003)
    • Tucson Arizona 85704 United States
    • Call for Information (Investigational Site 3603)
    • Tucson Arizona 85719 United States
    • Call for Information (Investigational Site 3543)
    • Fountain Valley California 92708 United States
    • Call for Information (Investigational Site 3553)
    • Fullerton California 92835 United States
    • Call for Information (Investigational Site 3539)
    • Loma Linda California 92350 United States
    • Call for Information (Investigational Site 3615)
    • Los Angeles California 90033 United States
    • Call for Information (Investigational Site 3521)
    • Los Angeles California 90095 United States
    • Call for Information (Investigational Site 3582)
    • Orange California 92868 United States
    • Call for Information (Investigational Site 8001)
    • Colorado Springs Colorado 80907 United States
    • Call for Information (Investigational Site 3592)
    • Denver Colorado 80205 United States
    • Call for Information (Investigational Site 3604)
    • Washington District of Columbia 20037 United States
    • Call for Information (Investigational Site 3600)
    • Fort Myers Florida 33901-8101 United States
    • Call for Information (Investigational Site 3584)
    • Miami Florida 33143 United States
    • Call for Information (Investigational Site 3599)
    • Saint Petersburg Florida 33705 United States
    • Call for Information (Investigational Site 3513)
    • Chicago Illinois 60611 United States
    • Call for Information (Investigational Site 3591)
    • Chicago Illinois 60612 United States
    • Call for Information (Investigational Site 3598)
    • Joliet Illinois 60436 United States
    • Call for Information (Investigational Site 8007)
    • Niles Illinois 60714 United States
    • Call for Information (Investigational Site 3506)
    • Peoria Illinois 61615 United States
    • Call for Information (Investigational Site 3596)
    • Skokie Illinois 60077 United States
    • Call for Information (Investigational Site 3505)
    • Scarborough Maine 04074 United States
    • Call for Information (Investigational Site 3540)
    • Baltimore Maryland 21201 United States
    • Call for Information (Investigational Site 3588)
    • Burlington Massachusetts 01805 United States
    • Call for Information (Investigational Site 3503)
    • Ann Arbor Michigan 48109-5936 United States
    • Call for Information (Investigational Site 3541)
    • Detroit Michigan 48202 United States
    • Call for Information (Investigational Site 3602)
    • Kansas City Missouri 64132 United States
    • Call for Information (Investigational Site 8009)
    • Omaha Nebraska 68130 United States
    • Call for Information (Investigational Site 3530)
    • Rochester New York 14642 United States
    • Call for Information (Investigational Site 3548)
    • Charlotte North Carolina 28204 United States
    • Call for Information (Investigational Site 3528)
    • Durham North Carolina 27710 United States
    • Call for Information (Investigational Site 3517)
    • Tulsa Oklahoma 74146 United States
    • Call for Information (Investigational Site 8005)
    • Springfield Oregon 97477 United States
    • Call for Information (Investigational Site 8011)
    • Tualatin Oregon 97062 United States
    • Call for Information (Investigational Site 3538)
    • Hershey Pennsylvania 17033 United States
    • Call for Information (Investigational Site 3583)
    • Philadelphia Pennsylvania 19104 United States
    • Call for Information (Investigational Site 3608)
    • Providence Rhode Island 02903 United States
    • Call for Information (Investigational Site 8000)
    • Greenville South Carolina 29615 United States
    • Call for Information (Investigational Site 3609)
    • Knoxville Tennessee 37920 United States
    • Call for Information (Investigational Site 3518)
    • Dallas Texas 75390-9110 United States
    • Call for Information (Investigational Site 8010)
    • Denton Texas 76210 United States
    • Call for Information (Investigational Site 8004)
    • Houston Texas 77024 United States
    • Call for Information (Investigational Site 3504)
    • Houston Texas 77030 United States
    • Call for Information (Investigational Site 8008)
    • San Antonio Texas 78217 United States
    • Call for Information (Investigational Site 3501)
    • Burlington Vermont 05401 United States
    • Call for Information (Investigational Site 3595)
    • Charlottesville Virginia 22903 United States
    • Call for Information (Investigational Site 8006)
    • Norfolk Virginia 23502 United States
    • Call for Information (Investigational Site 3544)
    • Everett Washington 98201 United States
    • Call for Information (Investigational Site 3587)
    • Seattle Washington 98109 United States
    • Merck Sharp & Dohme
    • Buenos Aires Argentina
    • MSD Belgium BVBA/SPRL
    • Brussels Belgium
    • MSD Brasil
    • Sao Paulo Brazil
    • Merck Canada
    • Kirkland Quebec H9H 4M7 Canada
    • Merck Sharp & Dohme (I.A.) Corp.
    • Santiago Chile
    • MSD France
    • Paris France
    • MSD Sharp & Dohme GmbH
    • Haar Germany
    • MSD Pharma Hungary Kft.
    • Budapest Hungary
    • MSD Ireland (Human Health) Ltd.
    • Dublin Ireland
    • Merck Sharp & Dohme Co. Ltd.
    • Hod Hasharon Israel
    • MSD Korea LTD
    • Seoul 4130 Korea, Republic of
    • Merck Sharp & Dohme BV
    • Haarlem Netherlands
    • Merck Sharp & Dohme IDEA, Inc.
    • Moscow Russian Federation
    • MSD (Pty) LTD South Africa
    • Midrand South Africa
    • Merck Sharp and Dohme de Espana S.A.
    • Madrid Spain
    • MSD (Thailand) Ltd.
    • Bangkok Thailand
    • Merck Sharp & Dohme Ilaclari Ltd. Sti
    • Istanbul Turkey
    • Merck Sharp & Dohme Ltd.
    • Hoddesdon United Kingdom

    View trial on ClinicalTrials.gov


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    Published April 11, 2017
  • A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Car

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    A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer


    Condition: Unresectable Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer

    Intervention:

    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Cisplatin + Gemcitabine
    • Drug: Carboplatin + Gemcitabine

    Purpose: This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03682068

    Sponsor: AstraZeneca

    Primary Outcome Measures:

    • Measure: Progression Free Survival (PFS)
    • Time Frame: approximately 4 years
    • Safety Issue:
    • Measure: Overall Survival (OS)
    • Time Frame: approximately 4 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall Survival at 24 months (OS24)
    • Time Frame: 24 months
    • Safety Issue:
    • Measure: Alive and Progression Free Survival at 12 months (APF12)
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Objective Response Rate (ORR)
    • Time Frame: approximately 4 years
    • Safety Issue:
    • Measure: Duration of Response (DoR)
    • Time Frame: approximately 4 years
    • Safety Issue:
    • Measure: Disease Control Rate (DCR)
    • Time Frame: approximately 4 years
    • Safety Issue:
    • Measure: Time from randomization to second (PFS2)
    • Time Frame: approximately 4 years
    • Safety Issue:
    • Measure: To assess disease-related symptoms, physical functioning, and other Health-related quality of life
    • Time Frame: Approximately 4 years
    • Safety Issue:

    Estimated Enrollment: 885

    Study Start Date: September 27, 2018

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum 99 Years
    • Gender: All

    Key Inclusion Criteria:

    • Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
    • Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
    • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
    • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
    • Adequate organ and marrow function as defined in the protocol
    • Life expectancy ≥12 weeks in the opinion of the investigator
    • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

    Key Exclusion Criteria:

    • Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
    • No severe concomitant condition that requires immunosuppression medication
    • Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
    • Patients who may be eligible for or are being considered for radical resection during the course of the study.
    • Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

    Contact:

    • AstraZeneca Clinical Study Information Center
    • 1-877-240-9479

    Locations:

    • Research Site
    • Birmingham Alabama 35294 United States
    • Research Site
    • Bakersfield California 93309 United States
    • Research Site
    • Fountain Valley California 92708 United States
    • Research Site
    • Fullerton California 92835 United States
    • Research Site
    • Los Angeles California 90095 United States
    • Research Site
    • Salinas California 93901 United States
    • Research Site
    • Santa Barbara California 93105 United States
    • Research Site
    • Santa Maria California 93454 United States
    • Research Site
    • Truckee California 96161 United States
    • Research Site
    • New Haven Connecticut 06520 United States
    • Research Site
    • Orlando Florida 32806 United States
    • Research Site
    • Chicago Illinois 60611 United States
    • Research Site
    • Fort Wayne Indiana 46808 United States
    • Research Site
    • Kansas City Kansas 66160 United States
    • Research Site
    • Louisville Kentucky 40202 United States
    • Research Site
    • New Orleans Louisiana 70112 United States
    • Research Site
    • Grand Rapids Michigan 49503 United States
    • Research Site
    • Bozeman Montana 59715 United States
    • Research Site
    • Livingston New Jersey 07039 United States
    • Research Site
    • Neptune New Jersey 07754 United States
    • Research Site
    • Bronx New York 10467 United States
    • Research Site
    • Lake Success New York 11042 United States
    • Research Site
    • New York New York 10029 United States
    • Research Site
    • New York New York 10065 United States
    • Research Site
    • Rochester New York 14642 United States
    • Research Site
    • Sioux Falls South Dakota 57104 United States
    • Research Site
    • Germantown Tennessee 38138 United States
    • Research Site
    • Fort Worth Texas 76104 United States
    • Research Site
    • Box Hill 3128 Australia
    • Research Site
    • Elizabeth Vale 5112 Australia
    • Research Site
    • Kogarah 2217 Australia
    • Research Site
    • Macquarie University 2109 Australia
    • Research Site
    • Murdoch 6150 Australia
    • Research Site
    • Orange 2800 Australia
    • Research Site
    • South Brisbane 4101 Australia
    • Research Site
    • St Albans 3021 Australia
    • Research Site
    • Curitiba 80810-050 Brazil
    • Research Site
    • Fortaleza 60336-232 Brazil
    • Research Site
    • Porto Alegre 90020-090 Brazil
    • Research Site
    • Porto Alegre 90610-000 Brazil
    • Research Site
    • Porto Alegre 91350-200 Brazil
    • Research Site
    • Ribeirão Preto 14048-900 Brazil
    • Research Site
    • Rio de Janeiro 20231-050 Brazil
    • Research Site
    • Rio de Janeiro 22793-080 Brazil
    • Research Site
    • Salvador 41950-640 Brazil
    • Research Site
    • Sao Paulo 01327-001 Brazil
    • Research Site
    • São José do Rio Preto 15090-000 Brazil
    • Research Site
    • São Paulo 01246-000 Brazil
    • Research Site
    • Burgas 8000 Bulgaria
    • Research Site
    • Pleven 5800 Bulgaria
    • Research Site
    • Plovdiv 4000 Bulgaria
    • Research Site
    • Sofia 1303 Bulgaria
    • Research Site
    • Sofia 1431 Bulgaria
    • Research Site
    • Sofia 1797 Bulgaria
    • Research Site
    • Varna 9010 Bulgaria
    • Research Site
    • Calgary Alberta T2N 4N2 Canada
    • Research Site
    • Edmonton Alberta T6G 1Z2 Canada
    • Research Site
    • Vancouver British Columbia V5Z 4E6 Canada
    • Research Site
    • Hamilton Ontario L8V 5C2 Canada
    • Research Site
    • Ottawa Ontario K1H 8L6 Canada
    • Research Site
    • Toronto Ontario M5G IX6 Canada
    • Research Site
    • Montreal Quebec H3T 1E2 Canada
    • Research Site
    • Beijing 100034 China
    • Research Site
    • Beijing 100191 China
    • Research Site
    • Beijing 100730 China
    • Research Site
    • Beijing China
    • Research Site
    • Changchun 130021 China
    • Research Site
    • Changsha 410008 China
    • Research Site
    • Changsha 410013 China
    • Research Site
    • Chongqing 400010 China
    • Research Site
    • Chongqing 400038 China
    • Research Site
    • Dalian 116027 China
    • Research Site
    • Guangzhou 510000 China
    • Research Site
    • Guangzhou 510060 China
    • Research Site
    • Hangzhou 310003 China
    • Research Site
    • Hangzhou 310009 China
    • Research Site
    • Hangzhou 310014 China
    • Research Site
    • Hangzhou 310022 China
    • Research Site
    • Jinan 250012 China
    • Research Site
    • Nanchang 330006 China
    • Research Site
    • Nanjing 2100008 China
    • Research Site
    • Nanjing 210009 China
    • Research Site
    • Shanghai 200032 China
    • Research Site
    • Shanghai 200072 China
    • Research Site
    • Shanghai 200127 China
    • Research Site
    • Shenyang 110001 China
    • Research Site
    • Suzhou 215006 China
    • Research Site
    • Tianjin 300211 China
    • Research Site
    • Urumqi 830000 China
    • Research Site
    • Xi'an 710061 China
    • Research Site
    • Xiamen 361003 China
    • Research Site
    • Brno 656 91 Czechia
    • Research Site
    • Hradec Kralove 500 05 Czechia
    • Research Site
    • Olomouc 779 00 Czechia
    • Research Site
    • Ostrava 708 52 Czechia
    • Research Site
    • Praha 2 128 08 Czechia
    • Research Site
    • Praha 140 59 Czechia
    • Research Site
    • Praha 180 81 Czechia
    • Research Site
    • Budapest 1062 Hungary
    • Research Site
    • Budapest 1122 Hungary
    • Research Site
    • Budapest 1145 Hungary
    • Research Site
    • Debrecen 4032 Hungary
    • Research Site
    • Györ 9024 Hungary
    • Research Site
    • Kecskemét 6000 Hungary
    • Research Site
    • Szolnok 5004 Hungary
    • Research Site
    • Ahmedabad 380060 India
    • Research Site
    • Gurgaon 122001 India
    • Research Site
    • Hubli 580025 India
    • Research Site
    • Hyderabad 500082 India
    • Research Site
    • Kolkata 700160 India
    • Research Site
    • Nagpur 440012 India
    • Research Site
    • Nasik 422005 India
    • Research Site
    • New Delhi 110063 India
    • Research Site
    • New Delhi 110085 India
    • Research Site
    • Pune 411004 India
    • Research Site
    • Vadodara 390007 India
    • Research Site
    • Haifa 31096 Israel
    • Research Site
    • Jerusalem 91120 Israel
    • Research Site
    • Kfar Saba 95847 Israel
    • Research Site
    • Petach-Tikva 4941492 Israel
    • Research Site
    • Ramat Gan 52621 Israel
    • Research Site
    • Arezzo 52100 Italy
    • Research Site
    • Milano 20133 Italy
    • Research Site
    • Napoli 80131 Italy
    • Research Site
    • Orbassano 10043 Italy
    • Research Site
    • Parma 43100 Italy
    • Research Site
    • Pavia 27100 Italy
    • Research Site
    • Roma 00100 Italy
    • Research Site
    • San Giovanni Rotondo 71013 Italy
    • Research Site
    • Terni 05100 Italy
    • Research Site
    • Verona 37134 Italy
    • Research Site
    • Bunkyo-ku 113-8603 Japan
    • Research Site
    • Chuo-ku 104-0045 Japan
    • Research Site
    • Fukuoka-shi 811-1347 Japan
    • Research Site
    • Hirosaki-shi 036-8563 Japan
    • Research Site
    • Kanazawa-shi 920-8641 Japan
    • Research Site
    • Kita-gun 761-0793 Japan
    • Research Site
    • Koshigaya-shi 343-8555 Japan
    • Research Site
    • Koto-ku 135-8550 Japan
    • Research Site
    • Kumamoto-shi 860-0008 Japan
    • Research Site
    • Kumamoto-shi 860-8556 Japan
    • Research Site
    • Kyoto-shi 606-8507 Japan
    • Research Site
    • Miyazaki-city 889-1692 Japan
    • Research Site
    • Nagasaki-shi 852-8501 Japan
    • Research Site
    • Nagoya-shi 466-8560 Japan
    • Research Site
    • Nagoya-shi 467-0001 Japan
    • Research Site
    • Niigata-shi 951-8520 Japan
    • Research Site
    • Osaka-shi 541-8567 Japan
    • Research Site
    • Osaka-shi 545-8586 Japan
    • Research Site
    • Osakasayama-shi 589-8511 Japan
    • Research Site
    • Shinjuku-ku 160-8582 Japan
    • Research Site
    • Suita-shi 565-0871 Japan
    • Research Site
    • Toyama-shi 930-0194 Japan
    • Research Site
    • Tsukuba-shi 305-8576 Japan
    • Research Site
    • Yokohama-shi 232-0024 Japan
    • Research Site
    • Yokohama-shi 241-8515 Japan
    • Research Site
    • Goyang-si 10408 Korea, Republic of
    • Research Site
    • Incheon 21565 Korea, Republic of
    • Research Site
    • Seoul 02841 Korea, Republic of
    • Research Site
    • Seoul 03722 Korea, Republic of
    • Research Site
    • Seoul 05505 Korea, Republic of
    • Research Site
    • Seoul 06351 Korea, Republic of
    • Research Site
    • Suwon-si 442-723 Korea, Republic of
    • Research Site
    • Bacolod 6100 Philippines
    • Research Site
    • Baguio City 2600 Philippines
    • Research Site
    • Cebu 6000 Philippines
    • Research Site
    • Davao City 8000 Philippines
    • Research Site
    • Makati 1229 Philippines
    • Research Site
    • Manila 1015 Philippines
    • Research Site
    • Quezon City 1101 Philippines
    • Research Site
    • Quezon City 1104 Philippines
    • Research Site
    • Bialystok 15-027 Poland
    • Research Site
    • Gdańsk 80-214 Poland
    • Research Site
    • Grudziądz 86-300 Poland
    • Research Site
    • Koszalin 75-581 Poland
    • Research Site
    • Kraków 31-501 Poland
    • Research Site
    • Olsztyn 10-228 Poland
    • Research Site
    • Poznan 60-693 Poland
    • Research Site
    • Radom 26-600 Poland
    • Research Site
    • Warszawa 02-781 Poland
    • Research Site
    • Ivanovo 153040 Russian Federation
    • Research Site
    • Krasnoyarsk 660133 Russian Federation
    • Research Site
    • Moscow 105229 Russian Federation
    • Research Site
    • Moscow 115280 Russian Federation
    • Research Site
    • Moscow 125284 Russian Federation
    • Research Site
    • Moscow 125367 Russian Federation
    • Research Site
    • Nizhniy Novgorod 603137 Russian Federation
    • Research Site
    • Omsk 644013 Russian Federation
    • Research Site
    • Rostov-on-Don 344037 Russian Federation
    • Research Site
    • Saint-Petersburg 195067 Russian Federation
    • Research Site
    • St. Petersburg 199178 Russian Federation
    • Research Site
    • St.-Petersburg, 198205 Russian Federation
    • Research Site
    • Vologda 160012 Russian Federation
    • Research Site
    • Barcelona 08908 Spain
    • Research Site
    • Barcelona 8003 Spain
    • Research Site
    • Barcelona 8035 Spain
    • Research Site
    • Lugo 27003 Spain
    • Research Site
    • Madrid 28007 Spain
    • Research Site
    • Madrid 28034 Spain
    • Research Site
    • Madrid 28040 Spain
    • Research Site
    • Malaga 29010 Spain
    • Research Site
    • Santander 39008 Spain
    • Research Site
    • Sevilla 41013 Spain
    • Research Site
    • Taichung 404 Taiwan
    • Research Site
    • Taichung 40705 Taiwan
    • Research Site
    • Tainan 704 Taiwan
    • Research Site
    • Taipei City 10050 Taiwan
    • Research Site
    • Taipei 11217 Taiwan
    • Research Site
    • Taoyuan 333 Taiwan
    • Research Site
    • Bangkok 10300 Thailand
    • Research Site
    • Bangkok 10400 Thailand
    • Research Site
    • Chom Thon 50200 Thailand
    • Research Site
    • Adana 1260 Turkey
    • Research Site
    • Adapazari 54290 Turkey
    • Research Site
    • Ankara 06590 Turkey
    • Research Site
    • Edirne 22030 Turkey
    • Research Site
    • Istanbul 34030 Turkey
    • Research Site
    • Izmir Turkey
    • Research Site
    • Ha Noi 100000 Vietnam
    • Research Site
    • Hanoi 100000 Vietnam
    • Research Site
    • Hanoi 100000 Vietnam
    • Research Site
    • Ho Chi Minh city 700000 Vietnam
    • Research Site
    • Ho Chi Minh city Vietnam
    • Research Site
    • Ho Chi Minh 700000 Vietnam

    View trial on ClinicalTrials.gov


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    Published February 20, 2019
  • A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy

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    A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy


    Condition: Hydronephrosis, Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant, Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant, Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant, Infiltrating Renal Pelvis Urothelial Carcinoma, Sarcomatoid Variant, Renal Pelvis Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage II Renal Pelvis Cancer AJCC v7, Stage II Ureter Cancer AJCC v7, Stage II Urethral Cancer AJCC v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Renal Pelvis Cancer AJCC v7, Stage III Ureter Cancer AJCC v7, Stage III Urethral Cancer AJCC v7, Stage IV Renal Pelvis Cancer AJCC v7, Stage IV Ureter Cancer AJCC v7, Stage IV Urethral Cancer AJCC v7, Ureter Urothelial Carcinoma, Urethral Urothelial Carcinoma

    Intervention:

    • Biological: Durvalumab
    • Procedure: Therapeutic Conventional Surgery
    • Biological: Tremelimumab

    Purpose: This pilot phase I trial studies the side effects of durvalumab and tremelimumab in treating patients with muscle-invasive, high-risk urothelial cancer that cannot be treated with cisplatin-based therapy before surgery. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02812420

    Sponsor: M.D. Anderson Cancer Center

    Primary Outcome Measures:

    • Measure: Incidence of adverse events determined by extreme toxicity
    • Time Frame: Up to 90 days after last dose of treatment
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Change in immune and molecular responses in peripheral blood and tumor tissues
    • Time Frame: Baseline to 17 weeks
    • Safety Issue:
    • Measure: Pathologic down-staging to T0 disease
    • Time Frame: Up to 1 year
    • Safety Issue:

    Estimated Enrollment: 45

    Study Start Date: March 7, 2017

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have tissue resected by transurethral resection of bladder tissue (TURBT) at the MD Anderson Cancer Center
    • Patients must have histologic proof of urothelial cancer; this includes bladder cancer, in addition to other tumors of the urothelial lining including renal pelvis, ureteral, and urethral cancer; upper tract urothelial carcinoma will also be included; this group may include any patient requiring cystectomy (or applicable surgery to resect tumors), including muscle invasive disease (cT2-3aN0M0), whose tumor could not be completely removed at transurethral resection
    • Patients with the following high-risk features who are not candidates for traditional neoadjuvant chemotherapy will be included for this trial: micropapillary, sarcomatoid and plasmacytoid features; 3-dimensional (3-D) mass on exam under anesthesia (EUA); lymphovascular invasion; hydronephrosis (unless in the opinion of the treating physician, this is not due to tumor); high grade (grade 3) tumors of the ureter, renal pelvis, or tumors in these areas with radiographic abnormality large enough to recognize as an abnormal mass by computed tomography (CT) or magnetic resonance imaging (MRI) imaging; direct invasion of the prostatic stroma or the vaginal wall (i.e. cT4a disease); patients who are candidates for but refusing conventional chemotherapy may be considered eligible; for patients in whom eligibility is unclear, final arbitration will be determined by the principal investigator
    • Subjects must have no prior exposure to immunotherapy, such as, but not limited to other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
    • Able and willing to give valid written consent for available archival tumor samples or fresh tumor biopsies/resections
    • Adequate organ and marrow function (subjects must not have received transfusions or growth factor support within 28 days prior to first dose)
    • Hemoglobin >= 9 g/dL
    • Absolute neutrophil count >= 1,000/mm^3
    • Platelet count >= 100,000/mm^3
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) except subjects with documented Gilbert's syndrome (> 3 x ULN), who must have a baseline total bilirubin =< 3.0 mg/dL
    • Subjects must be considered cisplatin ineligible as per treating physician due to renal dysfunction, or hearing impairment, or co-morbidities; cisplatin ineligibility defined as: glomerular filtration rate (GFR) less than 60 or; congestive heart failure (CHF) New York Heart Association (NYHA) class III or higher or; peripheral neuropathy grade 2 or higher or; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or higher or; impaired hearing; patient's refusal of traditional chemotherapy
    • Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician; periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception; they must also refrain from egg cell donation for 180 days after the final dose of investigational product
    • Nonsterilized males who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception from day 1 through 90 days after receipt of the final dose of investigational product; in addition, they must refrain from sperm donation for 90 days after the final dose of investigational product
    • Mild autoimmune conditions (such as localized psoriasis) requiring minimal treatment or systemic autoimmune conditions well controlled by target agents such as an anti-IL-17 that do not affect overall immune system; patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or conditions not expected to recur in the absence of an external trigger are allowed to participate

    Exclusion Criteria:

    • Concurrent enrollment in another clinical trial, unless in a follow-up period or it is an observational study
    • Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (e.g. insulin for diabetes and hormone replacement therapy) is acceptable
    • Any investigational anticancer therapy received within 28 days prior to the first dose of durvalumab and tremelimumab
    • Major surgical procedure (as defined by the principal investigator [PI] or co-PIs within 28 days prior to the first dose of durvalumab and tremelimumab or still recovering from prior surgery
    • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03 grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by durvalumab and tremelimumab may be included (e.g. hearing loss) after consultation with the principal investigator
    • Known or suspected autoimmune disease; patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study; patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate; any condition requiring systemic treatment with corticosteroids (> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug; inhaled steroids and adrenal replacement steroids doses > 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
    • History of primary immunodeficiency
    • Patients who have organ allografts
    • True active infections of hepatitis B, or C during screening
    • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    • Receipt of live, attenuated vaccine within 28 days prior to the first dose of durvalumab and tremelimumab (NOTE: subjects, if enrolled, should not receive live vaccine during the study and for 180 days after the last dose of both drugs)
    • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
    • Other invasive malignancies within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast, etc. that has/have been surgically cured
    • Any evidence of metastatic urothelial carcinoma
    • Known allergy or hypersensitivity to study drug formulations
    • Patient currently on dialysis

    Contact:

    • Jianjun Gao
    • 713-792-2830

    Location:

    • M D Anderson Cancer Center
    • Houston Texas 77030 United States

    View trial on ClinicalTrials.gov


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    Published October 25, 2017
  • A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma

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    A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma


    Condition: Localized Urothelial Carcinoma of the Renal Pelvis and Ureter, Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter, Regional Urothelial Carcinoma of the Renal Pelvis and Ureter

    Intervention:

    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin Hydrochloride
    • Drug: Cisplatin
    • Drug: Gemcitabine Hydrochloride
    • Drug: Carboplatin
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis

    Purpose: This phase II trial studies how well giving chemotherapy before surgery works in treating patients with aggressive upper urinary tract cancer. Drugs used in chemotherapy, such as methotrexate, vinblastine, doxorubicin hydrochloride, cisplatin, gemcitabine hydrochloride, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Removing the affected upper urinary tract by surgery is the recommended treatment for upper urinary tract cancer, but can cause loss of kidney function and prevent patients from being able to receive chemotherapy after surgery. Giving chemotherapy before surgery, when the kidneys are working at their maximum, may allow less tissue to be removed during surgery and may be more effective in treating patients with high grade upper urinary tract cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02412670

    Sponsor: ECOG-ACRIN Cancer Research Group

    Primary Outcome Measures:

    • Measure: pCR rates
    • Time Frame: Up to 5 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Recurrence-free survival
    • Time Frame: From the date of surgery to disease recurrence or death from any cause, assessed up to 5 years
    • Safety Issue:
    • Measure: Event-free survival
    • Time Frame: From registration to the earlier of recurrence, disease progression, new invasive primary cancer, or death from any cause, assessed up to 5 years
    • Safety Issue:
    • Measure: Bladder cancer-free survival
    • Time Frame: From the date of surgery to the earlier of a return of bladder cancer or death from any cause, assessed up to 5 years
    • Safety Issue:
    • Measure: Cancer-specific survival
    • Time Frame: From registration to death due to cancer, assessed up to 5 years
    • Safety Issue:
    • Measure: The proportion of patients with renal insufficiency (CrCl < 60 ml/min) post chemotherapy and post nephroureterectomy
    • Time Frame: Up to 60 days after completion of chemotherapy
    • Safety Issue:
    • Measure: The proportion of patients with renal function improvement (CrCl < 60 ml/min at baseline and CrCl >= 60 ml/min on study)
    • Time Frame: Up to 60 days after completion of chemotherapy
    • Safety Issue:
    • Measure: Distribution of changes in renal function post chemotherapy and post surgery
    • Time Frame: Baseline up to 60 days after completion of chemotherapy
    • Safety Issue:
    • Measure: Incidence of toxicities
    • Time Frame: Up to 30 days from date of surgery
    • Safety Issue:

    Estimated Enrollment: 60

    Study Start Date: April 2015

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have high grade upper tract urothelial carcinoma proven by one of the following:
    • Biopsy;
    • Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional imaging; or
    • Urinary cytology and a mass visualized during upper urinary tract endoscopy
    • Patients must have a creatinine clearance >= 30 ml/min as determined by Cockcroft-Gault calculation or 24-hour urine creatinine clearance measurement within 28 days of registration to be eligible for the study
    • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
    • Patients must have no evidence of metastatic disease or clinically enlarged lymph nodes on computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis and CT chest obtained within 28 days of registration (a negative biopsy is required for lymph nodes > 1 cm in size to confirm lack of involvement); patients with lymph nodes > 1 cm in whom a biopsy is deemed not feasible are not eligible; patients with elevated alkaline phosphatase or suspicious bone pain should also undergo baseline bone scans to evaluate for bone metastasis
    • Patients with any component of small cell carcinoma are not eligible; other variant histologies are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
    • Patients must not have peripheral neuropathy > grade 2
    • Patients must not have a history of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
    • Patients must have a left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition [MUGA] or 2-dimensional [2-D] echocardiogram) within 28 days of registration
    • Absolute neutrophil count (ANC) >= 1500/mm^3
    • Platelets >= 100,000/mm^3
    • Hemoglobin (HgB) >= 9
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2 X institutional upper limit of normal (ULN)
    • Bilirubin within institutional normal limits (or < 2.5 X the ULN for patients with Gilbert's disease)
    • Patients with concomitant primaries of the bladder/urethra are allowed, as long as these sites are surgically resected and non-invasive cancers (< cT1N0)
    • Patients must not have another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer; patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment
    • For patients who have creatinine clearance that meets >= 50 ml/min they must not have received prior systemic doxorubicin
    • Patients with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in last 3 months, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
    • Patients who are known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy are ineligible
    • Patients must have no prior radiation therapy to >= 25% of the bone marrow for other diseases or prior systemic anthracycline therapy; prior intravesical anthracycline therapy for non-muscle invasive urothelial carcinoma of the bladder is permitted
    • Patients may have a history of resectable urothelial cancer (including neoadjuvant chemotherapy) as long as patients meet one of the following:
    • pT0, Tis, or T1N0 and have no evidence of disease (NED) for more than 2 years from surgery or chemotherapy;
    • pT2-3aN0 and NED for more than 3 years from surgery or chemotherapy; or
    • > pT3b, or N+ and NED for more than 5 years from surgery or chemotherapy
    • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
    • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study

    Locations:

    • University of Alabama at Birmingham Cancer Center
    • Birmingham Alabama 35233 United States
    • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora Colorado 80045 United States
    • Memorial Hospital Colorado Springs
    • Colorado Springs Colorado 80909 United States
    • Poudre Valley Hospital
    • Fort Collins Colorado 80524 United States
    • Saint Francis Hospital and Medical Center
    • Hartford Connecticut 06105 United States
    • Beebe Medical Center
    • Lewes Delaware 19958 United States
    • Christiana Gynecologic Oncology LLC
    • Newark Delaware 19713 United States
    • Delaware Clinical and Laboratory Physicians PA
    • Newark Delaware 19713 United States
    • Helen F Graham Cancer Center
    • Newark Delaware 19713 United States
    • Medical Oncology Hematology Consultants PA
    • Newark Delaware 19713 United States
    • Regional Hematology and Oncology PA
    • Newark Delaware 19713 United States
    • Christiana Care Health System-Christiana Hospital
    • Newark Delaware 19718 United States
    • Beebe Health Campus
    • Rehoboth Beach Delaware 19971 United States
    • Nanticoke Memorial Hospital
    • Seaford Delaware 19973 United States
    • Christiana Care Health System-Wilmington Hospital
    • Wilmington Delaware 19801 United States
    • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah Georgia 31405 United States
    • Low Country Cancer Care Associates PC
    • Savannah Georgia 31405 United States
    • Saint Alphonsus Cancer Care Center-Boise
    • Boise Idaho 83706 United States
    • Saint Joseph Medical Center
    • Bloomington Illinois 61701 United States
    • Illinois CancerCare-Bloomington
    • Bloomington Illinois 61704 United States
    • Illinois CancerCare-Canton
    • Canton Illinois 61520 United States
    • Memorial Hospital of Carbondale
    • Carbondale Illinois 62902 United States
    • Illinois CancerCare-Carthage
    • Carthage Illinois 62321 United States
    • Centralia Oncology Clinic
    • Centralia Illinois 62801 United States
    • Carle on Vermilion
    • Danville Illinois 61832 United States
    • Cancer Care Center of Decatur
    • Decatur Illinois 62526 United States
    • Decatur Memorial Hospital
    • Decatur Illinois 62526 United States
    • Carle Physician Group-Effingham
    • Effingham Illinois 62401 United States
    • Crossroads Cancer Center
    • Effingham Illinois 62401 United States
    • Illinois CancerCare-Eureka
    • Eureka Illinois 61530 United States
    • Illinois CancerCare Galesburg
    • Galesburg Illinois 61401 United States
    • Western Illinois Cancer Treatment Center
    • Galesburg Illinois 61401 United States
    • Illinois CancerCare-Kewanee Clinic
    • Kewanee Illinois 61443 United States
    • Illinois CancerCare-Macomb
    • Macomb Illinois 61455 United States
    • Carle Physician Group-Mattoon/Charleston
    • Mattoon Illinois 61938 United States
    • Good Samaritan Regional Health Center
    • Mount Vernon Illinois 62864 United States
    • Illinois CancerCare-Ottawa Clinic
    • Ottawa Illinois 61350 United States
    • Radiation Oncology of Northern Illinois
    • Ottawa Illinois 61350 United States
    • Illinois CancerCare-Pekin
    • Pekin Illinois 61554 United States
    • Pekin Cancer Treatment Center
    • Pekin Illinois 61554 United States
    • Methodist Medical Center of Illinois
    • Peoria Illinois 61603 United States
    • OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
    • Peoria Illinois 61615-7827 United States
    • Illinois CancerCare-Peoria
    • Peoria Illinois 61615 United States
    • OSF Saint Francis Medical Center
    • Peoria Illinois 61637 United States
    • Illinois CancerCare-Peru
    • Peru Illinois 61354 United States
    • Valley Radiation Oncology
    • Peru Illinois 61354 United States
    • Illinois CancerCare-Princeton
    • Princeton Illinois 61356 United States
    • Central Illinois Hematology Oncology Center
    • Springfield Illinois 62702 United States
    • Southern Illinois University School of Medicine
    • Springfield Illinois 62702 United States
    • Springfield Clinic
    • Springfield Illinois 62703 United States
    • Memorial Medical Center
    • Springfield Illinois 62781 United States
    • Cancer Care Specialists of Illinois-Swansea
    • Swansea Illinois 62226 United States
    • Carle Cancer Center
    • Urbana Illinois 61801 United States
    • The Carle Foundation Hospital
    • Urbana Illinois 61801 United States
    • Franciscan Saint Anthony Health-Michigan City
    • Michigan City Indiana 46360 United States
    • Woodland Cancer Care Center
    • Michigan City Indiana 46360 United States
    • Reid Hospital and Health Care Services
    • Richmond Indiana 47374 United States
    • Oncology Hematology Care Inc-Crestview
    • Crestview Hills Kentucky 41017 United States
    • Ochsner Medical Center Jefferson
    • New Orleans Louisiana 70121 United States
    • Saint Joseph Mercy Hospital
    • Ann Arbor Michigan 48106-0995 United States
    • University of Michigan Comprehensive Cancer Center
    • Ann Arbor Michigan 48109 United States
    • Oakwood Hospital and Medical Center
    • Dearborn Michigan 48124 United States
    • Saint John Hospital and Medical Center
    • Detroit Michigan 48236 United States
    • Hurley Medical Center
    • Flint Michigan 48502 United States
    • Genesys Hurley Cancer Institute
    • Flint Michigan 48503 United States
    • Allegiance Health
    • Jackson Michigan 49201 United States
    • Sparrow Hospital
    • Lansing Michigan 48912 United States
    • Saint Mary Mercy Hospital
    • Livonia Michigan 48154 United States
    • Saint Joseph Mercy Oakland
    • Pontiac Michigan 48341 United States
    • Saint Joseph Mercy Port Huron
    • Port Huron Michigan 48060 United States
    • Saint Mary's of Michigan
    • Saginaw Michigan 48601 United States
    • Saint John Macomb-Oakland Hospital
    • Warren Michigan 48093 United States
    • Central Care Cancer Center-Carrie J Babb Cancer Center
    • Bolivar Missouri 65613 United States
    • Parkland Health Center-Bonne Terre
    • Bonne Terre Missouri 63628 United States
    • CoxHealth Cancer Center
    • Branson Missouri 65616 United States
    • Saint Francis Medical Center
    • Cape Girardeau Missouri 63703 United States
    • Southeast Cancer Center
    • Cape Girardeau Missouri 63703 United States
    • Capital Region Medical Center-Goldschmidt Cancer Center
    • Jefferson City Missouri 65109 United States
    • Freeman Health System
    • Joplin Missouri 64804 United States
    • Mercy Hospital-Joplin
    • Joplin Missouri 64804 United States
    • Phelps County Regional Medical Center
    • Rolla Missouri 65401 United States
    • Saint John's Clinic-Rolla-Cancer and Hematology
    • Rolla Missouri 65401 United States
    • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis Missouri 63109 United States
    • Missouri Baptist Medical Center
    • Saint Louis Missouri 63131 United States
    • Mercy Hospital Saint Louis
    • Saint Louis Missouri 63141 United States
    • Sainte Genevieve County Memorial Hospital
    • Sainte Genevieve Missouri 63670 United States
    • Mercy Hospital Springfield
    • Springfield Missouri 65804 United States
    • CoxHealth South Hospital
    • Springfield Missouri 65807 United States
    • Missouri Baptist Sullivan Hospital
    • Sullivan Missouri 63080 United States
    • Missouri Baptist Outpatient Center-Sunset Hills
    • Sunset Hills Missouri 63127 United States
    • Miami Valley Hospital South
    • Centerville Ohio 45459 United States
    • Oncology Hematology Care Inc-Eden Park
    • Cincinnati Ohio 45202 United States
    • Oncology Hematology Care Inc-Mercy West
    • Cincinnati Ohio 45211 United States
    • Oncology Hematology Care Inc - Anderson
    • Cincinnati Ohio 45230 United States
    • Oncology Hematology Care Inc - Kenwood
    • Cincinnati Ohio 45236 United States
    • Oncology Hematology Care Inc-Blue Ash
    • Cincinnati Ohio 45242 United States
    • Good Samaritan Hospital - Dayton
    • Dayton Ohio 45406 United States
    • Miami Valley Hospital
    • Dayton Ohio 45409 United States
    • Samaritan North Health Center
    • Dayton Ohio 45415 United States
    • Oncology Hematology Care Inc-Healthplex
    • Fairfield Ohio 45014 United States
    • Blanchard Valley Hospital
    • Findlay Ohio 45840 United States
    • Atrium Medical Center-Middletown Regional Hospital
    • Franklin Ohio 45005-1066 United States
    • Wayne Hospital
    • Greenville Ohio 45331 United States
    • Kettering Medical Center
    • Kettering Ohio 45429 United States
    • Springfield Regional Cancer Center
    • Springfield Ohio 45504 United States
    • Springfield Regional Medical Center
    • Springfield Ohio 45505 United States
    • Flower Hospital
    • Sylvania Ohio 43560 United States
    • Upper Valley Medical Center
    • Troy Ohio 45373 United States
    • University of Oklahoma Health Sciences Center
    • Oklahoma City Oklahoma 73104 United States
    • Tulsa Cancer Institute
    • Tulsa Oklahoma 74146 United States
    • Christiana Care Health System-Concord Health Center
    • Chadds Ford Pennsylvania 19317 United States
    • Geisinger Medical Center
    • Danville Pennsylvania 17822 United States
    • Geisinger Medical Center-Cancer Center Hazleton
    • Hazleton Pennsylvania 18201 United States
    • Geisinger Medical Oncology at Evangelical Community Hospital
    • Lewisburg Pennsylvania 17837 United States
    • Lewistown Hospital
    • Lewistown Pennsylvania 17044 United States
    • ECOG-ACRIN Cancer Research Group
    • Philadelphia Pennsylvania 19103 United States
    • Thomas Jefferson University Hospital
    • Philadelphia Pennsylvania 19107 United States
    • Geisinger Medical Oncology-Pottsville
    • Pottsville Pennsylvania 17901 United States
    • Geisinger Medical Group
    • State College Pennsylvania 16801 United States
    • Geisinger Wyoming Valley/Henry Cancer Center
    • Wilkes-Barre Pennsylvania 18711 United States
    • Medical University of South Carolina
    • Charleston South Carolina 29425 United States
    • Vanderbilt-Ingram Cancer Center Cool Springs
    • Franklin Tennessee 37067 United States
    • Vanderbilt Breast Center at One Hundred Oaks
    • Nashville Tennessee 37204 United States
    • Vanderbilt University/Ingram Cancer Center
    • Nashville Tennessee 37232 United States
    • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas Texas 75390 United States
    • Aurora Cancer Care-Burlington
    • Burlington Wisconsin 53105 United States
    • Aurora Cancer Care-Grafton
    • Grafton Wisconsin 53024 United States
    • Vince Lombardi Cancer Clinic-Marinette
    • Marinette Wisconsin 54143 United States
    • Aurora Advanced Healthcare Inc-Menomonee Falls
    • Menomonee Falls Wisconsin 53051 United States
    • Aurora Cancer Care-Milwaukee
    • Milwaukee Wisconsin 53209 United States
    • Vince Lombardi Cancer Clinic - Oshkosh
    • Oshkosh Wisconsin 54904 United States
    • Aurora Cancer Care-Racine
    • Racine Wisconsin 53406-5661 United States
    • Aurora Medical Center in Summit
    • Summit Wisconsin 53066 United States
    • Aurora Cancer Care-Waukesha
    • Waukesha Wisconsin 53188 United States

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • A Prospective, Non-Interventional Study to Assess the Prevalence of PD-L1 Expression in the First-Line Setting of Locally Advanced/Unresectable or Metastatic Urothelial Carcinoma

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    A Prospective, Non-Interventional Study to Assess the Prevalence of PD-L1 Expression in the First-Line Setting of Locally Advanced/Unresectable or Metastatic Urothelial Carcinoma


    Condition: Urothelial Carcinoma

    Purpose: The purpose of this study is to assess the prevalence of pre-treatment tumor tissue PD-L1 expression in patients diagnosed with advanced urothelial carcinoma.

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT03788746

    Sponsor: AstraZeneca

    Primary Outcome Measures:

    • Measure: Categorization of PD-L1 based on pre-treatment tissue samples collected at baseline
    • Time Frame: 24 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay
    • Time Frame: 24 months
    • Safety Issue:
    • Measure: To describe the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) as well as treatment patterns in the 1L setting of advanced UC
    • Time Frame: 54 months
    • Safety Issue:
    • Measure: To assess the association between pre-treatment tumor tissue PD-L1 expression with objective response, PFS, and OS among treated patients (anti PD-L1/PD-1, chemotherapy, other)
    • Time Frame: 60 months
    • Safety Issue:

    Estimated Enrollment: 250

    Study Start Date: January 17, 2019

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    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Provision of written informed consent
    • Age ≥18 years old
    • Patients with histologically-confirmed diagnosis of UC and healthcare provider (HCP)-confirmed advanced UC prior to or during 1L therapy (primary histology UC; mixed histologies are allowed). Where the 1L therapy setting is defined as:
    • Patients with no prior systemic therapy given for advanced UC; 1L is the first systemic therapy given for advanced UC
    • Patients who received neoadjuvant or adjuvant platinum-based chemotherapy with recurrence more than 12 months from the last chemotherapy dose
    • Patients with available tumor tissue sample (fresh or archival
    • up to 3 years old) that was collected as part of SoC any time prior to 1L treatment for advanced UC with a target of 18 slides available for biomarker testing (PD-L1 and tTMB).

    Exclusion Criteria:

    • Patients concurrently enrolled in other clinical trials that prohibit their participation in a non-interventional study
    • Patients with history of non-urothelial active malignancy that completed therapy within 2 years from study enrollment except:
    • Any resected in situ carcinoma or non-melanoma skin cancer
    • Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy) and in which no systemic therapy was indicated

    Contact:

    • AstraZeneca Clinical Study Information Center
    • 1-877-240-9479

    Locations:

    • Research Site
    • Little Rock Arkansas 72211 United States
    • Research Site
    • Glendale California 91206 United States
    • Research Site
    • Los Angeles California 90048 United States
    • Research Site
    • Los Angeles California 90067 United States
    • Research Site
    • Monterey California 93940 United States
    • Research Site
    • Santa Rosa California 95405 United States
    • Research Site
    • Denver Colorado 80211 United States
    • Research Site
    • Englewood Colorado 80113 United States
    • Research Site
    • Boca Raton Florida 33486 United States
    • Research Site
    • Hialeah Florida 33016 United States
    • Research Site
    • Augusta Georgia 30912 United States
    • Research Site
    • Elmhurst Illinois 60126 United States
    • Research Site
    • Harvey Illinois 60426 United States
    • Research Site
    • Lake Barrington Illinois 60010 United States
    • Research Site
    • Indianapolis Indiana 46256 United States
    • Research Site
    • Lafayette Indiana 47905 United States
    • Research Site
    • Muncie Indiana 47303 United States
    • Research Site
    • Cedar Rapids Iowa 52403 United States
    • Research Site
    • Waterloo Iowa 50703 United States
    • Research Site
    • Kansas City Kansas 66160 United States
    • Research Site
    • Wichita Kansas 67226 United States
    • Research Site
    • Baton Rouge Louisiana 70809 United States
    • Research Site
    • Shreveport Louisiana 71106 United States
    • Research Site
    • Bangor Maine 04401 United States
    • Research Site
    • Lewiston Maine 04240 United States
    • Research Site
    • Kalamazoo Michigan 49007 United States
    • Research Site
    • Saint Cloud Minnesota 56303 United States
    • Research Site
    • Bridgeton Missouri 63044 United States
    • Research Site
    • East Brunswick New Jersey 08816 United States
    • Research Site
    • Englewood New Jersey 07631 United States
    • Research Site
    • Freehold New Jersey 07728 United States
    • Research Site
    • Little Silver New Jersey 07739 United States
    • Research Site
    • Voorhees New Jersey 08043 United States
    • Research Site
    • Port Jefferson Station New York 11776 United States
    • Research Site
    • Dayton Ohio 45429 United States
    • Research Site
    • Knoxville Tennessee 37920 United States
    • Research Site
    • Nashville Tennessee 37209 United States
    • Research Site
    • Houston Texas 77005 United States
    • Research Site
    • Virginia Beach Virginia 23462 United States
    • Research Site
    • Olympia Washington 98506 United States
    • Research Site
    • Tacoma Washington 98684 United States

    View trial on ClinicalTrials.gov


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    Published August 23, 2019
  • A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL-7 (CYT107) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

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    A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL-7 (CYT107) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma


    Condition: Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8, Stage III Renal Pelvis Cancer AJCC v8, Stage III Ureter Cancer AJCC v8, Stage III Urethral Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8

    Intervention:

    • Drug: Atezolizumab
    • Biological: Glycosylated Recombinant Human Interleukin-7
    • Other: Laboratory Biomarker Analysis

    Purpose: This phase II trial studies how well atezolizumab when given with glycosylated recombinant human interleukin-7 (CYT107) works in treating participants with urothelial carcinoma that has spread to nearby tissue or lymph nodes, cannot be removed by surgery, or has spread to other places in the body. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. CYT107 is a biological product naturally made by the body that may stimulate the immune system to destroy tumor cells. Giving atezolizumab and CYT107 may work better in treating participants with locally advanced, inoperable, or metastatic urothelial carcinoma.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03513952

    Sponsor: National Cancer Institute (NCI)

    Primary Outcome Measures:

    • Measure: Objective response rate (ORR)
    • Time Frame: Up to 2 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Clinical benefit rate (CBR) measured by RECIST version (v.) 1.1 and immune-related (ir) RECIST
    • Time Frame: Up to 2 years
    • Safety Issue:
    • Measure: Progression-free survival (PFS)
    • Time Frame: Up to 2 years
    • Safety Issue:
    • Measure: Duration of response (DOR)
    • Time Frame: Up to 2 years
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: Up to 2 years
    • Safety Issue:

    Estimated Enrollment: 54

    Study Start Date: September 28, 2018

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra
    • Note: mixed histology tumors allowed if predominant histology is urothelial carcinoma
    • Note: small cell or neuroendocrine carcinoma is not allowed if predominant
    • Patients either may be treatment-naive and considered ineligible for cisplatin-based chemotherapy or have recurrent disease after any prior platinum-based chemotherapy regimen and meet at least one of the following criteria:
    • Glomerular filtration rate ≥ 30 mL/min and < 60 mL/min (by Cockcroft-Gault)
    • Grade 2 or higher hearing loss
    • Grade 2 or higher peripheral neuropathy
    • Eastern Cooperative Oncology Group (ECOG) performance status 2
    • OR have recurrent disease after any prior platinum-based chemotherapy regimen
    • Patients must have measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI)
    • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
    • Patients must have a life expectancy of greater or equal to 12 weeks
    • Leukocytes ≥ 2,500/mcL
    • Absolute neutrophil count ≥ 1,000/mcL
    • Platelets ≥ 100,000/mcL
    • Hemoglobin ≥ 8 g/dL
    • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (however, patients with known Gilbert's disease who have serum bilirubin level ≤ 3 × ULN may be enrolled)
    • Aspartate aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 × ULN (AST and/or ALT ≤ 5 × ULN for patients with liver involvement)
    • Alkaline phosphatase ≤ 2.5 × ULN (≤ 5 ± ULN for patients with documented liver involvement or bone metastases)
    • Creatinine clearance ≥ 30 mL/min/1.73 m^2 by Cockcroft-Gault
    • At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is < 30, and prevents patient enrollment on the trial
    • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
    • Patients must provide tissue from an archival tumor sample (obtained within 2 years from screening visit) or newly obtained core, punch, or excisional biopsy of a tumor lesion if deemed relatively safe and technically feasible
    • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of study agent(s); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
    • Patients must have the ability to understand and the willingness to sign a written informed consent document
    • Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
    • A stable regimen of highly active antiretroviral therapy (HAART)
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
    • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR) -based tests
    • Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma
    • Note: prior perioperative chemotherapy is allowed and is not counted as a line of therapy

    Exclusion Criteria:

    • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
    • Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) before the initiation of study treatment
    • Patients who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed:
    • Hormone-replacement therapy or oral contraceptives
    • Herbal therapy ≥ 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment)
    • Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment
    • Patients who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents
    • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
    • Minimum of 12 weeks from the first dose of anti-CTLA-4 and >6 weeks from the last dose
    • No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
    • Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment
    • Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
    • Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti TNF] agents) within 2 weeks before initiation of study treatment
    • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
    • The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
    • Patients taking bisphosphonate therapy for symptomatic hypercalcemia
    • Note: use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
    • Patients requiring treatment with a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor (e.g., denosumab) who cannot discontinue it before initiation of study treatment
    • Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
    • Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
    • Evaluable or measurable disease outside the CNS
    • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
    • No history of intracranial hemorrhage or spinal cord hemorrhage
    • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
    • No neurosurgical resection or brain biopsy within 28 days before initiation of study treatment
    • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
    • Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
    • No stereotactic radiation or whole-brain radiation within 28 days before initiation of study treatment
    • Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids
    • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
    • Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Patients with known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver/nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); and inherited liver disease
    • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
    • Patient who have a history or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
    • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible
    • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
    • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
    • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
    • Rash must cover less than 10% of body surface area (BSA)
    • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
    • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
    • Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
    • Patients who have known additional malignancies other than UBC within 2 years before initiation of study treatment; exceptions include malignancies with a negligible risk of metastasis or death and treated with expected curative outcome (e.g., non-melanomatous skin cancers), or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer
    • Patients with active tuberculosis (TB)
    • Patients who have leptomeningeal disease
    • Patients who have severe infections within 4 weeks before initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;
    • Exception: uncomplicated urinary tract infection will not be considered as a severe infection in these patients
    • Patients who have signs or symptoms of infection within 2 weeks before initiation of study treatment
    • Patients who have received oral or IV antibiotics within 2 weeks before initiation of study treatment; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
    • Patients who have major surgical procedure, other than for diagnosis, within 28 days before initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
    • Patients who have had a live, attenuated vaccine within 4 weeks before initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab.
    • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks before initiation of study treatment or at any time during the study
    • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction (within the last 6 months), or psychiatric illness/social situations that would limit compliance with study requirements
    • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g., infectious) illness

    Locations:

    • Kaiser Permanente-Riverside
    • Riverside California 92505 United States
    • Moffitt Cancer Center
    • Tampa Florida 33612 United States
    • University of Chicago Comprehensive Cancer Center
    • Chicago Illinois 60637 United States
    • East Jefferson General Hospital
    • Metairie Louisiana 70006 United States
    • Washington University School of Medicine
    • Saint Louis Missouri 63110 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • Seattle Cancer Care Alliance
    • Seattle Washington 98109 United States

    View trial on ClinicalTrials.gov


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    Published June 28, 2019
  • A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOT

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    A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-679/ECHO-302)


    Condition: Renal Cell Carcinoma (RCC)

    Intervention:

    • Drug: Pembrolizumab
    • Drug: Epacadostat
    • Drug: Sunitinib
    • Drug: Pazopanib

    Purpose: The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus epacadostat compared to sunitinib or pazopanib in participants with locally advanced/metastatic renal cell carcinoma (mRCC) with clear cell component who have not received prior systemic therapy for their mRCC.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03260894

    Sponsor: Incyte Corporation

    Primary Outcome Measures:

    • Measure: Progression-free survival of pembrolizumab + epacadostat versus standard of care (SOC)
    • Time Frame: Up to 30 months
    • Safety Issue:
    • Measure: Overall survival of pembrolizumab + epacadostat versus SOC
    • Time Frame: Up to 60 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Objective response rate of pembrolizumab + epacadostat versus SOC
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Duration of response of pembrolizumab + epacadostat versus SOC
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Safety and tolerability of pembrolizumab + epacadostat versus SOC as measured by number of participants experiencing adverse events (AEs)
    • Time Frame: Up to 39 months
    • Safety Issue:
    • Measure: Safety and tolerability of pembrolizumab + epacadostat versus SOC as measured by number of participants discontinuing study drug due to AEs
    • Time Frame: Up to 39 months
    • Safety Issue:
    • Measure: Health-related quality of life (HRQoL) of pembrolizumab + epacadostat versus SOC as measured by time to deterioration (TTD)
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: HRQoL of pembrolizumab + epacadostat versus SOC as measured by European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/quality of life scale
    • Time Frame: Up to 42 weeks
    • Safety Issue:
    • Measure: HRQoL of pembrolizumab + epacadostat versus SOC as measured by European Quality of Life (EuroQol) EQ-5D™ 3 level version (EQ 5D-3L) assessment
    • Time Frame: Up to 36 months
    • Safety Issue:

    Estimated Enrollment: 630

    Study Start Date: December 7, 2017

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features.
    • Must not have received any prior systemic therapy for their mRCC.
    • Measurable disease based on RECIST v1.1.
    • Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion as required.
    • Karnofsky performance status ≥ 70%.
    • Adequate organ function per protocol-defined criteria.

    Exclusion Criteria:

    • Use of protocol-defined prior/concomitant therapy.
    • Currently receiving or has received an investigational treatment as part of a study of an investigational agent or has used an investigational device within 4 weeks before randomization.
    • History of severe hypersensitivity reaction to study treatments or their excipients.
    • Active autoimmune disease that has required systemic treatment in past 2 years.
    • Known additional malignancy that has progressed or has required active treatment in the last 3 years.
    • Known active central nervous system metastases and/or carcinomatous meningitis.
    • History of (noninfectious) pneumonitis that required steroids or current pneumonitis.
    • History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful.
    • Significant cardiac event within 12 months before Cycle 1 Day 1.

    Contact:

    • Incyte Corporation Call Center (US)
    • 1.855.463.3463

    Locations:

    • Pinnacle Oncology Hematology
    • Scottsdale Arizona 85258 United States
    • Arizona Oncology Associates PC- HOPE
    • Tucson Arizona 85711 United States
    • Cedars-Sinai Medical Center
    • Los Angeles California 90048 United States
    • UC Irvine Comprehensive Cancer Center
    • Orange California 92868 United States
    • UC Davis Comprehensive Cancer Center
    • Sacramento California 95817 United States
    • Atlanta Cancer Care - Conyers
    • Conyers Georgia 30094 United States
    • Northwest Georgia Oncology Centers Pc
    • Marietta Georgia 30060 United States
    • Rush University Medical Center
    • Chicago Illinois 60612 United States
    • Dana Farber Cancer Institute
    • Boston Massachusetts 02215 United States
    • Southeast Nebraska Hematology & Oncology Consultants, P.C.
    • Lincoln Nebraska 68510 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10065 United States
    • Levine Cancer Institute
    • Charlotte North Carolina 28204 United States
    • University of Tennessee Erlanger Oncology & Hematology
    • Chattanooga Tennessee 37403 United States
    • The West Clinic, P.C.
    • Germantown Tennessee 38138 United States
    • US Oncology and Research
    • The Woodlands Texas 77380 United States
    • Utah Cancer Specialists
    • Salt Lake City Utah 84106 United States
    • Huntsman Cancer Institute
    • Salt Lake City Utah 84112 United States
    • Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
    • Roanoke Virginia 24014 United States
    • Shenandoah Oncology, P.C.
    • Winchester Virginia 22601 United States
    • Seattle Cancer Care Alliance
    • Seattle Washington 98019 United States
    • Canberra Hospital
    • Garran Australian Capital Territory 2605 Australia
    • Calvary Mater Newcastle
    • Waratah New South Wales 2298 Australia
    • Westmead Hospital
    • Westmead New South Wales 2145 Australia
    • Cabrini Health
    • Malvern Victoria 3144 Australia
    • Fiona Stanley Hospital
    • Murdoch 6150 Australia
    • Centro de pesquisa Porto Alegre
    • Porto Alegre Florianopolis 90610-000 Brazil
    • Fundacao Pio XII - Hospital de Cancer de Barretos
    • Barretos Sao Paulo 14784-400 Brazil
    • Instituto do Cancer de Sao Paulo - ICESP
    • São Paulo Sao Paulo 01246-000 Brazil
    • Hospital Sao Jose
    • São Paulo Sao Paulo 01321-001 Brazil
    • Centro Avancado de Tratamento Oncologico - CENANTRON -
    • Belo Horizonte 30130090 Brazil
    • Hospital de Clinicas de Porto Alegre
    • Porto Alegre 90035-903 Brazil
    • Tom Baker Cancer Centre
    • Calgary Alberta T2N 4N2 Canada
    • Kingston Health Sciences Centre - KGH Site
    • Kingston Ontario K7L 2V7 Canada
    • Sunnybrook Health Sciences, Odette Cancer Centre
    • Toronto Ontario M4N 3M5 Canada
    • CHUM - Hopital Notre-Dame
    • Montreal Quebec H2L 4M1 Canada
    • Jewish General Hospital
    • Montréal Quebec H3T 1E2 Canada
    • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
    • Quebec G1R 2J6 Canada
    • Clinica Alemana de Osorno
    • Osorno Region De Los Lagos 5311089 Chile
    • Fundacion Arturo Lopez Perez FALP
    • Santiago 7500921 Chile
    • Pontificia Universidad Catolica de Chile
    • Santiago 8320000 Chile
    • Hospital Clinico Vina del Mar
    • Vina del Mar 2520612 Chile
    • Centre Antoine Lacassagne
    • Nice Cedex 2 06189 France
    • CHU Besancon - Hopital Jean Minjoz
    • Besançon 25030 France
    • Hopital Saint Andre
    • Bordeaux 33075 France
    • Centre Francois Baclesse
    • Caen 14076 France
    • Hopital Prive Toulon Hyeres Sainte Marguerite
    • Hyeres 83400 France
    • Hopital Europeen Georges Pompidou
    • Paris 75015 France
    • Hospices Civils de Lyon Centre Hospitalier Lyon Sud
    • Pierre Benite 69495 France
    • Clinique Sainte Anne
    • Strasbourg 67000 France
    • CHU de Strasbourg - Nouvel Hopital Civil
    • Strasbourg 67091 France
    • Institut Gustave Roussy
    • Villejuif 94805 France
    • Helios Klinikum Berlin Buch
    • Berlin 13125 Germany
    • Universitaetsklinikum der Technischen Universitaet Dresden
    • Dresden 01307 Germany
    • Universitaetsklinikum Essen. Klinik und Poliklinik fuer Urologie
    • Essen 45147 Germany
    • Universitaetsklinikum Frankfurt
    • Frankfurt am Main 60590 Germany
    • Medizinische Hochschule Hannover
    • Hannover 30625 Germany
    • Universitaetsklinikum Jena
    • Jena 07747 Germany
    • Universitaetsklinikum Magdeburg. Klinik fuer Urologie
    • Magdeburg 39120 Germany
    • Universitaetsklinikum Tuebingen
    • Tuebingen 72076 Germany
    • Orszagos Onkologiai Intezet
    • Budapest Pest 1122 Hungary
    • Somogy Megyei Kaposi Mor Oktato Korhaz
    • Kaposvar 7400 Hungary
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
    • Miskolc 3526 Hungary
    • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet
    • Szolnok 5000 Hungary
    • Markusovszky Egyetemi Oktatokorhaz
    • Szombathely 9700 Hungary
    • Zala Megyei Szent Rafael Korhaz
    • Zalaegerszeg 8900 Hungary
    • Adelaide & Meath Hospital
    • Dublin 00024 Ireland
    • University Hospital Waterford
    • Waterford X91ER8E Ireland
    • National Cancer Center Hospital East
    • Kashiwa Chiba 277-8577 Japan
    • Sapporo Medical University Hospital
    • Sapporo Hokkaido 060-8543 Japan
    • Hokkaido University Hospital
    • Sapporo Hokkaido 060-8648 Japan
    • Nara Medical University Hospital
    • Kashihara Nara 634-8522 Japan
    • Kindai University Hospital
    • Osakasayama Osaka 589-8511 Japan
    • Yamaguchi University Hospital
    • Ube Yamaguchi 755-8505 Japan
    • Niigata University Medical & Dental Hospital
    • Niigata 951-8520 Japan
    • Toranomon Hospital
    • Tokyo 105-8470 Japan
    • Nippon Medical School Hospital
    • Tokyo 113-8603 Japan
    • Keio University Hospital
    • Tokyo 160-8582 Japan
    • Chonnam National University Hwasun Hospital
    • Hwasun Jeollanam Do 58128 Korea, Republic of
    • Severance Hospital Yonsei University Health System
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 06351 Korea, Republic of
    • Auckland City Hospital
    • Auckland Grafton 1023 New Zealand
    • Helse Bergen HF Haukeland sykehus
    • Bergen 5053 Norway
    • Sykehuset Oestfold
    • Gralum 1714 Norway
    • Sorlandet sykehus HF
    • Kristiansand 4615 Norway
    • Akershus University Hospital
    • Lørenskog 1478 Norway
    • Oslo universitetssykehus
    • Oslo 0450 Norway
    • Universitetssykehuset i Nord Norge. Kreftavdelingen
    • Tromsø 9019 Norway
    • St Olavs Hospital
    • Trondheim 7030 Norway
    • Ivanovo regional oncology dispensary
    • Ivanovo 153040 Russian Federation
    • Russian Scientific Center of Roentgenoradiology
    • Moscow 117997 Russian Federation
    • Central Hospital with Out-patient Clinic of Pres Aff Dept
    • Moscow 121359 Russian Federation
    • National Medical Research Radiology Centre
    • Moscow 125284 Russian Federation
    • Bashkortostan Republican Clinical Oncology Dispensary
    • Ufa 450054 Russian Federation
    • Hospital Parc Tauli
    • Sabadell Barcelona 08208 Spain
    • Hospital Germans Trias i Pujol
    • Badalona 08916 Spain
    • Hospital del Mar
    • Barcelona 08003 Spain
    • Hospital General Universitario Gregorio Maranon
    • Madrid 28007 Spain
    • Hospital Universitario HM Sanchinarro
    • Madrid 28050 Spain
    • Hospital Clinico Universitario de Santiago
    • Santiago de Compostela 15706 Spain
    • Instituto Valenciano de Oncologia
    • Valencia 46009 Spain
    • Chang Gung Med Foundation. Kaohsiung Branch
    • Kaohsiung 833 Taiwan
    • China Medical University Hospital
    • Taichung 40447 Taiwan
    • National Cheng Kung University Hospital
    • Tainan 70457 Taiwan
    • National Taiwan University Hospital
    • Taipei 10048 Taiwan
    • Taipei Veterans General Hospital
    • Taipei 112 Taiwan
    • Baskent Universitesi Adana Dr. Turgut Noyan Uygulama ve Arastirma Merkezi
    • Adana 01250 Turkey
    • Ankara Numune Education and Research Hospital
    • Ankara 06100 Turkey
    • Hacettepe University Medical Faculty
    • Ankara 06100 Turkey
    • Istanbul Universitesi Onkoloji Enstitusu
    • Istanbul 34093 Turkey
    • Istanbul Medeniyet Universitesi Goztepe EAH
    • Istanbul 34732 Turkey
    • Ege Universitesi Tıp Fakultesi
    • Izmir 35040 Turkey
    • Namik Kemal Universitesi Tip Fakultesi
    • Tekirdag 59100 Turkey
    • MI Kryviy Rih Center of Dnipropetrovsk Regional Council
    • Kryvyi Rih Dnipropetrovsk Region 50048 Ukraine
    • Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov
    • Dnipropetrovs'k 49005 Ukraine
    • Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC
    • Dnipropetrovs'k 49102 Ukraine
    • MI Precarpathian Clinical Oncology Center
    • Ivano-Frankivs'k 76018 Ukraine
    • RMI Sumy Regional Clinical Oncology Dispensary
    • Sumy 40022 Ukraine
    • The Royal Marsden NHS Foundation Trust.
    • Sutton Surrey SM2 5PT United Kingdom
    • Western General Hospital
    • Edinburgh EH4 2XU United Kingdom
    • Beatson Institute of Cancer Research
    • Glasgow G12 0YN United Kingdom
    • Barts Health NHS Trust - St Bartholomew s Hospital
    • London EC1A 7BE United Kingdom
    • The Royal Marsden Foundation Trust
    • London SW3 6JJ United Kingdom
    • The Christie NHS Foundation Trust
    • Manchester MB204BX United Kingdom

    View trial on ClinicalTrials.gov


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    Published January 21, 2018
  • A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy

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    A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy


    Condition: Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms, Renal Pelvis Neoplasms, Urothelial Cancer, Ureteral Neoplasms, Urethral Neoplasms

    Intervention:

    • Drug: Enfortumab vedotin

    Purpose: This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer. This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect. Patients who sign up for this trial must also fall into one of these categories: - Patients have already received treatment with platinum-containing chemotherapy - Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03219333

    Sponsor: Astellas Pharma Global Development, Inc.

    Primary Outcome Measures:

    • Measure: Objective response rate (ORR) by an independent review facility (IRF)
    • Time Frame: Up to 3 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Duration of response (DOR) by an IRF
    • Time Frame: Up to 7.5 years
    • Safety Issue:
    • Measure: Disease control rate at 16 weeks (DCR16) by an IRF
    • Time Frame: 16 weeks
    • Safety Issue:
    • Measure: Progression free survival (PFS) by an IRF
    • Time Frame: Up to 7.5 years
    • Safety Issue:
    • Measure: ORR by investigator assessment
    • Time Frame: Up to 7.5 years
    • Safety Issue:
    • Measure: DOR by investigator assessment
    • Time Frame: Up to 7.5 years
    • Safety Issue:
    • Measure: DCR16 by investigator assessment
    • Time Frame: 16 weeks
    • Safety Issue:
    • Measure: Progression free survival (PFS) by investigator assessment
    • Time Frame: Up to 7.5 years
    • Safety Issue:
    • Measure: Overall survival (OS)
    • Time Frame: Up to 7.5 years
    • Safety Issue:
    • Measure: Incidence of adverse events (AEs)
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: Incidence of laboratory abnormalities
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax)
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: PK parameter for enfortumab vedotin: Trough concentration (Ctrough)
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: PK parameter for monomethyl auristatin E (MMAE): Cmax
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: PK parameter for MMAE: Ctrough
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: PK parameter for Total Antibody (TAb): Cmax
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: PK parameter for Total Antibody (TAb): Ctrough
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:
    • Measure: Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin
    • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
    • Safety Issue:

    Estimated Enrollment: 200

    Study Start Date: October 8, 2017

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
    • Metastatic disease or locally advanced disease that is not resectable.
    • Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
    • Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
    • Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
    • Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
    • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
    • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2.
    • Anticipated life expectancy of ≥3 months as assessed by the investigator.

    Exclusion Criteria:

    • Ongoing sensory or motor neuropathy Grade ≥2.
    • Active central nervous system (CNS) metastases.
    • Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
    • Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
    • Uncontrolled tumor-related pain or impending spinal cord compression.

    Contact:

    • Seattle Genetics Trial Information Support
    • 866-333-7436

    Locations:

    • Alaska Urological Institute
    • Anchorage Alaska 99503 United States
    • Mayo Clinic Arizona
    • Scottsdale Arizona 85259 United States
    • Arizona Oncology Associates, PC - HOPE
    • Tucson Arizona 85710 United States
    • University of California Davis
    • Davis California 95616 United States
    • Keck Medical Center / University of Southern California
    • Los Angeles California 90033 United States
    • Keck Medical Center / Newport Beach
    • Newport Beach California 92663 United States
    • Kaiser Permanente Oakland
    • Oakland California 94611 United States
    • Chao Family Comprehensive Cancer Center University of California Irvine
    • Orange California 92868 United States
    • University of California Irvine - Newport
    • Orange California 92868 United States
    • Kaiser Permanente Roseville
    • Roseville California 95661 United States
    • Kaiser Permanente Sacramento
    • Sacramento California 95825 United States
    • Kaiser Permanente San Francisco
    • San Francisco California 94115 United States
    • Kaiser Permanente San Jose
    • San Jose California 95119 United States
    • Kaiser Permanente San Leandro
    • San Leandro California 94577 United States
    • Kaiser Permanente Santa Clara
    • Santa Clara California 95051 United States
    • Kaiser Permanente South San Francisco
    • South San Francisco California 94080 United States
    • Kaiser Permanente Medical Center Northern California
    • Vallejo California 94589 United States
    • Kaiser Permanente Walnut Creek
    • Walnut Creek California 94596 United States
    • Rocky Mountain Cancer Centers - Aurora
    • Aurora Colorado 80012 United States
    • Yale Cancer Center
    • New Haven Connecticut 06520 United States
    • Ocala Oncology Center
    • Ocala Florida 34471 United States
    • H. Lee Moffitt Cancer Center & Research Institute
    • Tampa Florida 33612 United States
    • Augusta University
    • Augusta Georgia 30912 United States
    • University of Chicago
    • Chicago Illinois 60637-1470 United States
    • Norton Cancer Institute
    • Louisville Kentucky 40202 United States
    • Johns Hopkins Medical Center
    • Baltimore Maryland 21231 United States
    • Maryland Oncology Hematology, P.A.
    • Silver Spring Maryland 20904 United States
    • Massachusetts General Hospital
    • Boston Massachusetts 02114 United States
    • Dana Farber Cancer Institute
    • Boston Massachusetts 02215 United States
    • Karmanos Cancer Institute / Wayne State University
    • Detroit Michigan 48201 United States
    • Washington University School of Medicine
    • Saint Louis Missouri 63110 United States
    • Comprehensive Cancer Centers of Nevada
    • Las Vegas Nevada 89169 United States
    • New York Oncology Hematology, P.C.
    • Albany New York 12206 United States
    • New York University (NYU) Cancer Institute
    • New York New York 10016 United States
    • Columbia University Medical Center
    • New York New York 10022 United States
    • Mount Sinai Medical Center
    • New York New York 10029 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10087-9049 United States
    • James P. Wilmot Cancer Center / University of Rochester Medical Center
    • Rochester New York 14642 United States
    • Duke University Medical Center
    • Durham North Carolina 27710 United States
    • Cleveland Clinic, The
    • Cleveland Ohio 44195 United States
    • James Cancer Hospital / Ohio State University
    • Columbus Ohio 43210 United States
    • Northwest Cancer Specialists, P.C.
    • Tualatin Oregon 97062 United States
    • Thomas Jefferson University
    • Philadelphia Pennsylvania 19107 United States
    • Hillman Cancer Center / University of Pittsburgh Medical Center
    • Pittsburgh Pennsylvania 15232 United States
    • Greenville Health System Cancer Institute
    • Greenville South Carolina 29615 United States
    • Vanderbilt University Medical Center
    • Nashville Tennessee 37204 United States
    • Texas Oncology - Austin Central
    • Austin Texas 78731 United States
    • Texas Oncology - Baylor Sammons Cancer Center
    • Dallas Texas 75246 United States
    • Houston Methodist Cancer Center
    • Houston Texas 77030 United States
    • University of Virginia
    • Charlottesville Virginia 22908 United States
    • Virginia Cancer Specialists, PC
    • Fairfax Virginia 22031 United States
    • Virginia Oncology Associates
    • Norfolk Virginia 23502 United States
    • Seattle Cancer Care Alliance / University of Washington
    • Seattle Washington 98109-1023 United States
    • Site FR33001
    • Villejuif-Cedex-France France
    • Site DE49004
    • Muenster Germany
    • Site DE49001
    • Tübingen Germany
    • Site IT39001
    • Milano Italy
    • Site IT39003
    • Terni Italy
    • Site JP81001
    • Hirosaki Aomori Japan
    • Site JP81004
    • Tsukuba Ibaraki Japan
    • Site JP81002
    • Morioka Iwate Japan
    • Site JP81008
    • Osakasayama Osaka Japan
    • Site JP81006
    • Shinjuku-ku Tokyo Japan
    • Site JP81009
    • Ube Yamaguchi Japan
    • Site JP81005
    • Chiba Japan
    • Site JP81011
    • Fukuoka Japan
    • Site JP81012
    • Fukuoka Japan
    • Site JP81003
    • Nigata Japan
    • Site JP81007
    • Osaka Japan
    • Site JP81010
    • Tokushima Japan
    • Site KR82005
    • Daejeon Korea, Republic of
    • Site KR82003
    • Seongnam-si Korea, Republic of
    • Site KR82001
    • Seoul Korea, Republic of
    • Site KR82002
    • Seoul Korea, Republic of
    • Site KR82004
    • Seoul Korea, Republic of
    • Site NL31001
    • Amsterdam Netherlands
    • Site ES34002
    • Barcelona Spain
    • Site ES34003
    • Santander Spain
    • Site ES34004
    • Sevilla Spain

    View trial on ClinicalTrials.gov


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    Published July 28, 2019
  • An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma

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    An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma


    Condition: Urothelial Carcinoma

    Intervention:

    • Drug: Rogaratinib (BAY1163877)
    • Drug: Atezolizumab
    • Drug: Placebo

    Purpose: FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study comprises two separate parts: Phase 1b (Part A) and Phase 2 (Part B).The study parts differ in design, objectives and treatment. The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability,RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients. The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma. Of note, patients who participate in Part A are not allowed to participate in Part B. Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03473756

    Sponsor: Bayer

    Primary Outcome Measures:

    • Measure: Number of subjects with Dose-limiting toxicities(DLTs) in Part A
    • Time Frame: Up to 21 days
    • Safety Issue:
    • Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part A
    • Time Frame: Up to 5 months
    • Safety Issue:
    • Measure: Number of subjects with drug-related TEAEs in Part A
    • Time Frame: Up to 5 months
    • Safety Issue:
    • Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part A
    • Time Frame: Up to 5 months
    • Safety Issue:
    • Measure: Progression Free Survival(PFS)
    • Time Frame: Up to 25 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Objective Response Rate(ORR) in Part A
    • Time Frame: Up to 5 months
    • Safety Issue:
    • Measure: Maximal plasma concentration (Cmax) of rogaratinib in Part A
    • Time Frame: At cycle 1 Day 1
    • Safety Issue:
    • Measure: Area under the curve(0-8) (AUC(0-8)) of rogaratinib in Part A
    • Time Frame: At cycle 1 Day 1
    • Safety Issue:
    • Measure: Disease Control Rate(DCR) in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Duration of Response(DOR) in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Overall Survival(OS) in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Objective Response Rate (ORR) in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Concentrations for rogaratinib in Part B
    • Time Frame: Cycle 1 Day 1(C1D1), C2D1, C3D1, C4D1, C5D1
    • Safety Issue:
    • Measure: Concentrations for atezolizumab in Part B
    • Time Frame: C1D1, C1D15
    • Safety Issue:
    • Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Number of subjects with drug-related TEAEs in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part B
    • Time Frame: Up to 25 months
    • Safety Issue:
    • Measure: Number of subjects with significant change in vital signs, physical finding and clinical laboratory results
    • Time Frame: Up to 25 months
    • Safety Issue:

    Estimated Enrollment: 210

    Study Start Date: May 15, 2018

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression testing
    • High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+) in archival or fresh tumor biopsy specimen
    • Documented locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
    • No prior systemic treatment for locally advanced or metastatic urothelial carcinoma. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. Prior local intra-vesical chemotherapy or prior local immunotherapy is allowed if completed at least 4 weeks before the first study drug administration. Regionally available standard of care options must be considered for all patients.
    • Ineligibility for cisplatin-based chemotherapy as defined by any one of the following criteria:
    • Impaired renal function (GFR > 30 but < 60 mL/min/1.73 m2) according to the modification of diet in renal disease (MDRD) abbreviated formula
    • A Hearing loss (measured by audiometry) of > 25 dB at two contiguous test frequencies in at least one ear.
    • Grade ≥ 2 peripheral neuropathy (i.e. sensory alteration or paresthesia including tingling)
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1. Exlusion criteria:
    • Active symptomatic or untreated brain metastases as determined by CT or MRI evaluation during screening and prior radiographic assessment.
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    • History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
    • Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms of angina at rest) or
    • New-onset angina (within last 3 months before the first study drug administration)
    • Myocardial infarction (MI) within past 6 months before the first study drug administration
    • Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.
    • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or known left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
    • Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.
    • Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia).
    • Concomitant therapies that are known to increase serum calcium or phosphate levels (i.e. antacids, phosphate-containing laxatives oral/rectal, potassium phosphate) and that cannot be discontinued or switched to a different medication before the first study drug administration
    • Treatment with systemic corticosteroids or other systemic immunosuppressant medications within 2 weeks before the first study drug administration, or anticipated requirement for systemic immunosuppressive medications during the trial.

    Contact:

    • Bayer Clinical Trials Contact
    • (+) 1-888-8422937

    Locations:

    • University of Arizona Cancer Center
    • Tucson Arizona 85724 United States
    • University of California - Davis
    • Sacramento California 95817 United States
    • Comprehensive Cancer Center
    • Chicago Illinois 60637 United States
    • Barbara Ann Karmanos Cancer Institute
    • Detroit Michigan 48201 United States
    • Memorial Sloan-Kettering Cancer Center
    • New York New York 10065 United States
    • Krankenhaus der Elisabethinen Linz GmbH
    • Linz Oberösterreich 4020 Austria
    • Uniklinikum Salzburg - Landeskrankenhaus
    • Salzburg 5020 Austria
    • Krankenhaus der Barmherzigen Brüder
    • Wien 1020 Austria
    • Allgemeines Krankenhaus der Stadt Wien
    • Wien 1090 Austria
    • Institut Bergonié - Unicancer Nouvelle Aquitaine
    • Bordeaux Cedex 33076 France
    • Centre Oscar Lambret - Lille
    • Lille Cedex 59020 France
    • Centre René Gauducheau - Nantes
    • Nantes 44805 France
    • Eberhard-Karls-Universität Tübingen
    • Tübingen Baden-Württemberg 72076 Germany
    • Universitätsklinikum Essen
    • Essen Nordrhein-Westfalen 45122 Germany
    • Universitätsklinikum Köln
    • Köln Nordrhein-Westfalen 50937 Germany
    • Universitätsmedizin der Johannes Gutenberg Universität Mainz
    • Mainz Rheinland-Pfalz 55131 Germany
    • A.O.U. di Modena - Policlinico
    • Modena Emilia-Romagna 41124 Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano Lombardia 20133 Italy
    • IRCCS Istituto Europeo di Oncologia (IEO)
    • Milano Lombardia 20141 Italy
    • IRCCS Istituto Oncologico Veneto (IOV)
    • Padova Veneto 35128 Italy
    • A.O.U.I. Verona
    • Verona Veneto 37134 Italy
    • National Cancer Center Hospital East
    • Kashiwa Chiba 277-8577 Japan
    • National Hospital Organization Shikoku Cancer Center
    • Matsuyama Ehime 791-0280 Japan
    • University of Tsukuba Hospital
    • Tsukuba Ibaraki 305-8576 Japan
    • The Cancer Institute Hospital of JFCR
    • Koto-ku Tokyo 135-8550 Japan
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 06351 Korea, Republic of
    • Yonsei University College of Medicine
    • Seoul 120-752 Korea, Republic of
    • Ciutat Sanitària i Universitaria de la Vall d'Hebron
    • Barcelona 08035 Spain
    • Hospital Clínic i Provincial de Barcelona
    • Barcelona 08036 Spain
    • Hospital de la Santa Creu i de Sant Pau
    • Barcelona 08041 Spain
    • Hospital Ramón y Cajal
    • Madrid 28034 Spain
    • Hospital General Universitario de Valencia
    • Valencia 46014 Spain

    View trial on ClinicalTrials.gov


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    Published June 28, 2019
  • An Open Label Phase II Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma

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    An Open Label Phase II Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma


    Condition: Urothelial Carcinoma

    Intervention:

    • Drug: tipifarnib

    Purpose: Platinum-based chemotherapy is now regarded a standard first-line treatment for patients with advanced urothelial carcinoma (UC). However, patients who failed to response or experienced progression after platinum-based chemotherapy have a grim prognosis and a standard salvage treatment is not available. UC is known to harbor multiple mutations. In the investigators' own high-throughput molecular profiling study, the most commonly observed mutations included TP53, FGFR3(fibroblast growth factor receptor 3 ) and HRAS. Since RAS signaling can be attenuated using selective farnesyl transferase (FTase) inhibitors, tipifarnib, a highly potent and selective inhibitor of FTase, was proposed to be an effective therapeutic approach in the treatment of UC.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02535650

    Sponsor: Samsung Medical Center

    Primary Outcome Measures:

    • Measure: Response rate
    • Time Frame: Up to 12 months for each subject
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Duration of response
    • Time Frame: Up to 12 months for each subject
    • Safety Issue:
    • Measure: Progression-free survival
    • Time Frame: Up to 12 months for each subject
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: Until the date of death from any cause, whichever came first, assessed up to 1 year 6 months.
    • Safety Issue:
    • Measure: Safety and Tolerability
    • Time Frame: Up to 12 months for each subject
    • Safety Issue:

    Estimated Enrollment: 18

    Study Start Date: November 12, 2015

    Phase: Phase 2

    Eligibility:

    • Age: minimum 20 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Subject is at least 20 years of age.
    2. Subject has a histologically or cytologically confirmed diagnosis of urothelial carcinoma arising from urinary bladder or upper urinary tract.
    3. Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available.
    4. Subject has a tumor that carries a missense HRAS mutation according to a standard methodology using Illumina HiSeqTM. (Any mutation)HRAS status may have been assessed either in primary tumor tissue, recurrent or metastatic disease.
    5. Subject has consented to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status.
    6. Must have a life expectancy of 3 months or more
    7. Subject has measurable disease according to RECIST(Response Evaluation Criteria in Solid Tumors ) v1.1 and has relapsed (progressive disease) or is refractory to prior therapy.
    8. At least 2 weeks since the last systemic therapy regimen prior to enrolment. Subjects must have recovered to NCI CTCAE v. 4.03 < Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
    9. At least 2 weeks since last radiotherapy if radiation was localized to the only site of measurable disease, unless there is documentation of disease progression of the irradiated site. Patients must have recovered from all acute toxicities from radiotherapy.
    10. ECOG(Eastern Cooperative Oncology Group ) performance status of 0 or
    11. Acceptable liver function:
    12. Bilirubin ≤ 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert's syndrome diagnosed as per institutional guidelines.
    13. AST (SGOT,aspartate aminotransferase ) and ALT (SGPT,Alanine aminotransferase) ≤ 3 x ULN; if liver metastases are present, then ≤ 5 x ULN is allowed.
    14. Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or MDRD(Modification of Diet in Renal Disease ) formulas. Serum potassium with normal or ≤ CTCAE Grade 1 with or without supplementation.
    15. Acceptable hematologic status (without growth factor support or transfusion dependency):
    16. ANC(absolute neutrophil count )>1500 cells/μL.
    17. Platelet count >100,000/μL.
    18. Hemoglobin >9.0 g/dL.
    19. Female subjects must be either:
    20. Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
    21. If of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child-bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
    22. Not breast feeding at any time during the study.
    23. Written and voluntary informed consent understood, signed and dated.

    Exclusion Criteria:

    1. Ongoing treatment with an anticancer agent not contemplated in this protocol.
    2. Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
    3. Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebrovascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
    4. Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Subjects that develop brain metastasis during the study may have their treatment interrupted to receive a course of cranial radiation and restart trial medication after a recovery period of at least 1 week. High dose corticosteroids may be employed for the management of cranial radiation but must be tapered off before resuming treatment.
    5. Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day
    6. Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery.
    7. Double primary cancer of other site(s), except for cured ones at the discretion of investigator
    8. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
    9. Subjects who have exhibited allergic reactions to tipifarnib, structural compounds similar to tipifarnib or to its excipients.
    10. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
    11. The subject has legal incapacity or limited legal capacity.
    12. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.
    13. QTcF interval ≥ 470 msecs

    Contact:

    • Se hoon Park, MD,Ph.D.
    • 2-3410-3459 Ext. 82

    Location:

    • Samsung Medical Center
    • Seoul 135710 Korea, Republic of

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • An Open Label, Multicenter, Single Arm Phase II Study to Evaluate the Activity and Tolerability of the Novel mTOR Inhibitor, MLN0128 (TAK-228), in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract Whose Tumor

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    An Open Label, Multicenter, Single Arm Phase II Study to Evaluate the Activity and Tolerability of the Novel mTOR Inhibitor, MLN0128 (TAK-228), in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract Whose Tumors Harbor a TSC1 and/or a TSC2 Mutation


    Condition: Locally Advanced Bladder Urothelial Carcinoma, Metastatic Transitional Cell Carcinoma, Metastatic Urothelial Carcinoma, Recurrent Bladder Carcinoma, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage IV Bladder Urothelial Carcinoma AJCC v7

    Intervention:

    • Other: Laboratory Biomarker Analysis
    • Drug: Sapanisertib

    Purpose: This pilot phase II trial studies how well sapanisertib works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) with tuberous sclerosis (TSC)1 and/or TSC2 mutations (changes in deoxyribonucleic acid [DNA]). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03047213

    Sponsor: National Cancer Institute (NCI)

    Primary Outcome Measures:

    • Measure: Overall response rate (TSC1 patients)
    • Time Frame: Up to 4 weeks after last dose of study treatment
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence of toxicity (TSC1 patients)
    • Time Frame: Up to 4 weeks after last dose of study treatment
    • Safety Issue:
    • Measure: Progression-free survival (PFS) (TSC1 patients)
    • Time Frame: Time from start of treatment to date of progression or death, whichever occurs first, assessed up to 1 year
    • Safety Issue:
    • Measure: Overall survival (OS) (TSC1 patients)
    • Time Frame: Time from start of treatment to time of death from any cause, assessed up to 1 year
    • Safety Issue:

    Estimated Enrollment: 209

    Study Start Date: December 1, 2016

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
    • Must have a histologically confirmed transitional cell carcinoma (TCC, also known as urothelial carcinoma), locally advanced or metastatic
    • Patient must have TCCs tumors harboring a TSC1 or TSC2 mutation identified by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
    • Unless the pre-screening was performed at Yale Clinical Molecular Pathology Lab (YCMPL), patients must have TCC tumor tissue available for submission in a form of at least 10 unstained slides or formalin-fixed paraffin-embedded (FFPE) block (FFPE block highly recommended and preferred) along with a buccal swab; if the number of slides is less than 10, a biopsy should be considered; if a biopsy is deemed unsafe, the case may be discussed with the study principal investigator (PI) and approval must be given for eligibility
    • Patient must have developed disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], methotrexate-vinblastine-doxorubicin-cisplatin [MVAC], carboplatin, gemcitabine [CarboGem]) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or must be unfit or ineligible for cisplatin-based chemotherapy; there is no restriction on the number of prior lines of chemotherapeutics agents received
    • Patients who progressed within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant regimen are considered second-line patients; therefore, these patients may be also eligible
    • Patients who are unfit or ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria are eligible for this trial:
    • Eastern Cooperative Oncology Group (ECOG) performance score of 2
    • Creatinine clearance < 60 mL/min
    • A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies
    • Grade >= 2 peripheral neuropathy
    • ECOG performance status =< 2 (Karnofsky >= 60 %)
    • Life expectancy of greater than 12 weeks
    • Hemoglobin >= 9 g/dL
    • Fasting serum glucose =< 130 mg/dL
    • Glycosylated hemoglobin measurement (HbA1c) < 7.0%
    • Fasting triglycerides =< 300 mg/dL
    • Leukocytes >= 3,000/mcL
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • Total bilirubin within normal institutional limits
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal (ULN) and =< 5 ULN if liver metastases are present
    • Creatinine =< 1.5 x upper normal institutional limits (UNL) OR creatinine clearance >= 40 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour)
    • Patients with controlled diabetes are allowed on study; controlled diabetes is defined as fasting blood sugar (FBS) = 130 mg/dL or less, and patients whose FBS can be brought in this range with medical therapy are eligible for trial inclusion
    • The effects of MLN0128 (TAK-228) on the developing human fetus are unknown; fertility and developmental studies with MLN0128 (TAK-228) have not been conducted; on the basis of potential hazard of other mTOR inhibitors (i.e., rapamycin and other rapalogs) on the developing fetus, women of childbearing age should avoid becoming pregnant while taking any mTOR inhibitor including MLN0128 (TAK-228)
    • Female patients must:
    • Be postmenopausal for at least 1 year before the screening visit, OR
    • Be surgically sterile, OR
    • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling [e.g., United States product insert [USPI], summary of product characteristics [SmPC], etc.;]) after the last dose of study drug, OR
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient; NOTE: periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception; female and male condoms should not be used together
    • Male patients, even if surgically sterilized (i.e., status postvasectomy), must:
    • Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (NOTE: periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception; female and male condoms should not be used together)
    • AND agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
    • Ability to swallow oral medications
    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Patients who have had chemotherapy, immunotherapy, or investigational therapy, within 4 weeks (6 weeks for nitrosoureas or mitomycin C), or palliative radiotherapy within 2 weeks prior to the first dose of the study drug
    • Patients who have not recovered from adverse events due to prior anti-cancer therapy to grade 1 or baseline; patients with stable, controlled grade 2 adverse events (AEs) such as peripheral neuropathy, hypothyroidism, hypertension, adrenal insufficiency or alopecia are allowed after discussing with the PI
    • Patients with known symptomatic, untreated central nervous system (including brain, spinal cord)
    • Patients who have a history of brain/central nervous system (CNS) metastasis are eligible for the study provided that all the following criteria are met:
    • Brain/CNS metastases which have been treated
    • No evidence of disease progression for >= 3 months before the first dose of study drug
    • No hemorrhage after treatment
    • Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228
    • No ongoing requirement for dexamethasone or anti-epileptic drugs
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN0128 (TAK-228)
    • Subjects who are on systemic corticosteroids (intravenous (IV) or oral steroids, excluding inhaled, topical or ophthalmic corticosteroids), or anti-epileptic drugs for treated brain metastasis
    • Subjects taking strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C19 or CYP2C9 within 1 week preceding the first dose of MLN0128 (TAK-228); if a subject requires treatment with strong inhibitors and/or inducers of CYP3A4, CYP2C19 and/or CYP2C9, alternative treatment must be considered; if no alternative is available, one such medication may be allowed after discussing with the study principle investigator
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding rate controlled atrial fibrillation/flutter), or psychiatric illness/social situations that would limit compliance with study requirements
    • Pregnant and breastfeeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MLN0128 (TAK-228)
    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; however, HIV patients treated with regimens that have low cytochrome P450 (CYP450) inhibition may be allowed as long as the patient's general health and cluster of differentiation (CD)4 counts are within acceptable levels
    • Patients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)
    • Patients with untreated or active hepatitis B or C infection
    • Significant active cardiovascular or pulmonary disease at the time of study entry, including
    • Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
    • Pulmonary hypertension
    • Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air
    • Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement
    • Medically significant (symptomatic) bradycardia
    • Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228)
    • Concomitant administration of any proton pump inhibitor (PPI) is not permitted during the study; patients receiving PPI therapy before enrollment must stop using the PPI for 7 days before their first dose of study drugs
    • History of any of the following within the last 6 months prior to study entry:
    • Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
    • Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures
    • Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
    • Pulmonary embolism
    • New York Heart Association (NYHA) class III or IV heart failure
    • Placement of a pacemaker for control of rhythm
    • Subjects who have initiated treatment with bisphosphonates less than 30 days prior to the first administration of MLN0128 (TAK-228); concurrent bisphosphonate use is only allowed if the bisphosphonate was initiated at least 30 days prior to the first administration of MLN0128 (TAK-228)
    • Patients who received prior PI3K, AKT or mTOR inhibitors are not allowed
    • Patients who received radiation therapy within the last 4 weeks; radiation exposure may not exceed 30% of marrow area

    Locations:

    • Los Angeles County-USC Medical Center
    • Los Angeles California 90033 United States
    • USC / Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States
    • Keck Medical Center of USC Pasadena
    • Pasadena California 91105 United States
    • University of California Davis Comprehensive Cancer Center
    • Sacramento California 95817 United States
    • Smilow Cancer Center/Yale-New Haven Hospital
    • New Haven Connecticut 06510 United States
    • Yale University
    • New Haven Connecticut 06520 United States
    • Northwestern University
    • Chicago Illinois 60611 United States
    • University of Kansas Clinical Research Center
    • Fairway Kansas 66205 United States
    • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore Maryland 21287 United States
    • Massachusetts General Hospital Cancer Center
    • Boston Massachusetts 02114 United States
    • Brigham and Women's Hospital
    • Boston Massachusetts 02115 United States
    • Beth Israel Deaconess Medical Center
    • Boston Massachusetts 02215 United States
    • Dana-Farber Cancer Institute
    • Boston Massachusetts 02215 United States
    • University of Michigan Comprehensive Cancer Center
    • Ann Arbor Michigan 48109 United States
    • Nebraska Medicine-Bellevue
    • Bellevue Nebraska 68123 United States
    • Nebraska Medicine-Village Pointe
    • Omaha Nebraska 68118 United States
    • University of Nebraska Medical Center
    • Omaha Nebraska 68198 United States
    • UNC Lineberger Comprehensive Cancer Center
    • Chapel Hill North Carolina 27599 United States
    • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh Pennsylvania 15232 United States
    • Vanderbilt Breast Center at One Hundred Oaks
    • Nashville Tennessee 37204 United States
    • Vanderbilt University/Ingram Cancer Center
    • Nashville Tennessee 37232 United States
    • Huntsman Cancer Institute/University of Utah
    • Salt Lake City Utah 84112 United States

    View trial on ClinicalTrials.gov


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    Published May 2, 2019
  • An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.

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    An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.


    Condition: Urothelial Bladder Carcinoma

    Intervention:

    • Drug: Pembrolizumab (MK-3475)

    Purpose: Patients with T2-T4a N0 urothelial bladder carcinoma (UBC) with residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence) will receive 3 cycles of pembrolizumab (MK-3475) at the dose of 200mg 3 weekly prior to surgery (radical cystectomy). Cystectomy will be planned to be done within 3 weeks of the last dose (accounting for a total of 9 weeks). Computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan will be done during screening and before surgery. After cystectomy, patients with the evidence of pathologic stage T3-4 (pT3-4) and/or pathologically node-positive disease will be managed according to local guidelines. Further anti programmed-death (PD)-1 or anti PD-ligand 1 (PD-L1) therapy will not be given post-operatively. PD-L1 status will be centralized and assessed on TURB specimen using an anti-PD-L1 antibody (Ab) and a prototype immunohistochemical (IHC) assay. PD-L1 positivity will be defined as any staining in the stroma or in ≥1% of tumor cells. Pathologic complete response (pCR) is the primary endpoint. All patients enrolled who receive at least 1 cycle of study drug will be includes in the intention-to-treat (ITT) analysis. The alternative hypothesis (H1) is pCR ≥20% and null hypothesis (H0) pCR≤10%. A 2-stage design will be used to estimate the number of pts required. Out of 90 pts overall, with the first stage of 49 pts, ≥6 pCR will be required in the first stage, and ≥13 pCR in the whole study population (80% power and a 2-sided test of significance at the 10% level). Correlative research on tissue/blood samples will include immune-cell profiling in tumor and blood during Pembrolizumab, cytokine assessment, and molecular profiling of tumor samples.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02736266

    Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

    Primary Outcome Measures:

    • Measure: Pathologic complete response
    • Time Frame: At the time of radical cystectomy (within 9 weeks of the first dose of pembrolizumab)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Adverse events
    • Time Frame: Up to 2 years
    • Safety Issue:
    • Measure: Percentage of treatment-related delay in surgery
    • Time Frame: Starting at week 9
    • Safety Issue:
    • Measure: Frequency of treatment-related adverse events
    • Time Frame: Up to 1 year
    • Safety Issue:

    Estimated Enrollment: 90

    Study Start Date: February 27, 2017

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Willing and able to provide written informed consent.
    2. Ability to comply with the protocol.
    3. Age ≥ 18 years.
    4. Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
    5. Fit and planned for cystectomy (according to local guidelines).
    6. Clinical stage T2-T4a N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1).
    7. Residual disease after TURB (surgical opinion, cystoscopy or radiological presence).
    8. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site and determined to be evaluable for tumor PD-L1 expression prior to study enrolment; patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with Merck representatives.
    9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
    10. Adequate hematologic and end-organ function tests.

    Exclusion Criteria:

    • Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry.
    • Previously intravenous chemotherapy bladder cancer. Patients who have previously had radiotherapy or concurrent chemo-radiation would be eligible.
    • Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
    • Evidence of measurable nodal or metastatic disease.
    • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
    • Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
    • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
    • Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
    • Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the pembrolizumab formulation
    • History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    • Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
    • Patients with uncontrolled Type 1 diabetes mellitus
    • Uncontrolled hypercalcemia
    • Patients with prior allogeneic stem cell or solid organ transplantation.
    • History of idiopathic pulmonary fibrosis
    • Positive test for HIV.
    • Patients with active hepatitis infection
    • Patients with active tuberculosis.
    • Prior treatment with anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody or pathway-targeting agents.
    • Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study
    • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
    • History of severe immune-related adverse effects from anti−CTLA-4 (CTCAE Grade 3 and 4).
    • Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.

    Contact:

    • Andrea Necchi, MD
    • +390223902402

    Location:

    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano Mi 20133 Italy

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • An Open-label, Randomized, Phase 1 Safety and Pharmacokinetic Study of Enfortumab Vedotin (ASG-22CE) in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma

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    An Open-label, Randomized, Phase 1 Safety and Pharmacokinetic Study of Enfortumab Vedotin (ASG-22CE) in Japanese Patients With Locally Advanced or Metastatic Urothelial Carcinoma


    Condition: Metastatic Urothelial Cancer

    Intervention:

    • Drug: Enfortumab vedotin

    Purpose: The objective of this study is to assess the safety, tolerability and pharmacokinetics of enfortumab vedotin (ASG-22CE) when administered intravenously to Japanese subjects with locally advanced or metastatic urothelial carcinoma. This study will also assess the immunogenicity as defined by the incidence of anti-drug antibody (ADA) and anti-tumor activity of enfortumab vedotin (ASG-22CE) when administered intravenously to Japanese subjects with locally advanced or metastatic urothelial carcinoma.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03070990

    Sponsor: Astellas Pharma Inc

    Primary Outcome Measures:

    • Measure: Safety assessed by incidence of adverse events
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Safety assessed by laboratory tests: Hematology
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Safety assessed by laboratory tests: Biochemistry
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Safety assessed by laboratory tests: Urinalysis
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Safety assessed by laboratory tests: Coagulation studies
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI)
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for TAb: Maximum observed concentration (Cmax)
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for ADC: Cmax
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for MMAE: Cmax
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for TAb: Trough concentration (Ctrough)
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for ADC: Ctrough
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for MMAE: Ctrough
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for TAb: Time to maximum concentration (Tmax)
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for ADC: Tmax
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for MMAE: Tmax
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for ADC: AUC0-7
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for MMAE: AUC0-7
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for ADC: t1/2
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:
    • Measure: PK parameter for MMAE: t1/2
    • Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence of Anti-Drug Antibody (ADA)
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Overall Response Rate
    • Time Frame: Up to 12 months
    • Safety Issue:
    • Measure: Disease Control Rate
    • Time Frame: Up to 12 months
    • Safety Issue:

    Estimated Enrollment: 17

    Study Start Date: April 24, 2017

    Phase: Phase 1

    Eligibility:

    • Age: minimum 20 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Subject must have histologically confirmed, locally advanced (TNM classification T3b and any N; or T and N2-3) or metastatic Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
    • Subject must be able to submit a tumor tissue samples for Nectin-4 expression analysis at central laboratory.
    • Subject must have failed at least one prior chemotherapy regimen for advanced disease. Urothelial and bladder cancer subjects are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy.
    • Subject must have measurable disease according to Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1).
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    Exclusion Criteria:

    • Preexisting sensory neuropathy Grade ≥ 2.
    • Preexisting motor neuropathy Grade ≥ 2.
    • Uncontrolled central nervous system metastasis that requires active treatment.
    • Any anticancer therapy within 14 days prior to the first dose of study drug.
    • Subjects with pre-existing immunotherapy-related adverse events requiring high doses of systemic steroids are not eligible.

    Locations:

    • Site JP00003
    • Tsukuba Ibaraki Japan
    • Site JP00005
    • Sendai Miyagi Japan
    • Site JP00008
    • Suita Osaka Japan
    • Site JP00004
    • Chuo-ku Tokyo Japan
    • Site JP00007
    • Koto-ku Tokyo Japan
    • Site JP00006
    • Fukuoka Japan
    • Site JP00001
    • Niigata Japan
    • Site JP00002
    • Okayama Japan

    View trial on ClinicalTrials.gov


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    Published November 13, 2019
  • Familial and Atypical Urothelial Cancer Registry

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    Familial and Atypical Urothelial Cancer Registry


    Condition: Urothelial Cancer, Renal Pelvis Cancer, Ureter Cancer, Bladder Cancer

    Intervention:

    • Other: saliva sample and questionaire
    • Other: saliva sample, questionaire

    Purpose: This study is being done to create a registry to help us learn more about urinary and other cancers. This will let us look at large groups of people who do and do not have this kind of cancer. The investigators will look at risk factors to learn more about how these impact cancer. The investigators will also look at genetic markers. These are genes that are found in a known place. They are often associated with a particular trait. If the gene changes in some way, it may predict cancer or response to treatment. The investigators will look for markers in your saliva. This registry will help us develop better methods of: Preventing these cancers. Diagnosing these cancers. Treating these cancers.

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT00902590

    Sponsor: Memorial Sloan Kettering Cancer Center

    Primary Outcome Measures:

    • Measure: Determine whether single nucleotide polymorphisms in regions discovered from whole genome scans, such as 8q24 & chromosome 3, & candidate genes, include NAT2 & GSTM1, prev found to be assoc with bladder ca risk, are assoc with UC in this study population
    • Time Frame: 2 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: To determine whether single nucleotide polymorphisms in the genes and regions listed above are associated with outcomes after UC diagnosis in the population
    • Time Frame: 2 years
    • Safety Issue:

    Estimated Enrollment: 3200

    Study Start Date: May 2009

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    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Urothelial Cancer Cases
    • Must be ≥ 18 years of age AND
    • Must have a diagnosis of urothelial cancer AND
    • Must be an English-speaker Non-Cancer Control Group
    • Must be ≥ 18 years of age AND
    • Must not have cancer or a personal history of cancer, with the exception of skin cancer. AND
    • Must not be a blood relative of cases AND
    • Must not be a blood relative of another control AND
    • Must be an English-speaker Family Member Control Group: In select kindreds with a high prevalence of bladder cancer and/or very early onset bladder cancer, first- and second-degree family members of probands may be contacted by the MSKCC study team and invited to complete the questionnaire and submit a saliva sample.
    • Must be ≥ 18 years of age AND
    • Must be a blood relative of a case participant AND
    • Must be an English-speaker

    Exclusion Criteria:

    • Have any condition, which in the opinion of the primary MSKCC clinician or investigators precludes their ability to provide informed consent.

    Contact:

    • Dean Bajorin, MD
    • 646-422-4333

    Locations:

    • Memorial Sloan Kettering Basking Ridge
    • Basking Ridge New Jersey 07920 United States
    • Memorial Sloan Kettering Commack
    • Commack New York 11725 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10065 United States
    • Memorial Sloan Kettering Nassau
    • Uniondale New York 11553 United States

    View trial on ClinicalTrials.gov


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    Published December 12, 2016
  • From the Desk of Evan Yu: PD-1 or PD-L1 Inhibition for Front-Line Metastatic Urothelial Cancer.

    With the recent regulatory approvals of PD-1 and PD-L1 antibodies for patients with metastatic urothelial cancer, we have significantly expanded treatment options for this patient population.  Atezolizumab is a PD-L1 antibody that not only demonstrated significant responses but has also shown durability of response and clinical benefit through stable disease in a substantial proportion of patients in the post-platinum treated setting, leading to FDA approval in May 2016.1 
    Published April 11, 2017
  • Molecular Correlates of Sensitivity and Resistance to Therapy in Genitourinary Malignancy

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    Molecular Correlates of Sensitivity and Resistance to Therapy in Genitourinary Malignancy


    Condition: Healthy Control, Localized Urothelial Carcinoma of the Renal Pelvis and Ureter, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Soft Tissues, Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter, Recurrent Bladder Carcinoma, Recurrent Prostate Carcinoma, Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter, Stage IV Bladder Cancer, Stage IV Bladder Urothelial Carcinoma, Stage IV Prostate Cancer

    Intervention:

    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis

    Purpose: This research trial collects and studies tissue and blood samples from patients with prostate or bladder/urothelial cancer that has recurred (come back) at or near the same place as the original (primary) tumor or has spread to other parts of the body. Studying samples of blood and tissue samples from patients with prostate or bladder/urothelial cancer in the laboratory may help doctors learn more about new biomarkers, potential drug targets, and resistance developing in response to treatment. It may also help doctors find better ways to treat the cancer.

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT01050504

    Sponsor: University of Washington

    Primary Outcome Measures:

    • Measure: DNA genomic sequencing
    • Time Frame: Up to 6 years
    • Safety Issue:
    • Measure: Gene expression profile using microarray assays
    • Time Frame: Up to 6 years
    • Safety Issue:
    • Measure: Mutation mapping using the OncoMap and other genotyping techniques
    • Time Frame: Up to 6 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Expression of androgen metabolic enzymes by quantitative real time-polymerase chain reaction
    • Time Frame: Up to 6 years
    • Safety Issue:
    • Measure: Proteomic profile
    • Time Frame: Up to 6 years
    • Safety Issue:

    Estimated Enrollment: 300

    Study Start Date: August 2009

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    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: Male

    Inclusion Criteria:

    • Patients with localized and/or metastatic bladder/urothelial or prostate cancer who have disease in the primary organ, biopsy accessible bone metastases (collaborating radiologists will determine if bone metastasis is appropriate for biopsy) or soft tissue metastases are eligible; men and women without cancer are eligible to have blood or normal tissue collected if acquired as part of non-research procedures (e.g. transurethral resection of the prostate or bladder); in patients without malignancy, no additional tissue beyond that necessary for care will be procured
    • Ability to adequately understand and give informed consent
    • Local or metastatic disease to soft tissue or bone at sites accessible to biopsy with minimal risk of complications Or the ability to obtain tissue with minimal risk of complication from a surgical procedure being conducted as a part of another research study Or for standard of care purposes or patients who have archival tissue collected for research or standard of care who are willing to donate archival tissue for this study
    • Alternatively, men and women without cancer or who are at risk of developing cancer are eligible to have blood or normal tissue collected if acquired; tissue will only be acquired as part of non-research procedures (e.g. transurethral resection of the prostate or bladder; in patients without malignancy, no additional tissue beyond that necessary for care will be procured
    • Platelet count > 50,000
    • White blood cell (WBC) > 1,500
    • Hemoglobin (Hgb) > 8.0
    • International normalized ratio (INR) < 1.5
    • Partial thromboplastin time (PTT) < 45
    • No history of excessive unexplained bleeding from previous surgery

    Exclusion Criteria:

    • Patients unable to stop chronic anticoagulation with warfarin or Lovenox for less than 3 days
    • Serious or uncontrolled infection
    • Treatment with a vascular endothelial growth factor (VEGF) inhibitor (such as Avastin) within the past 28 days

    Location:

    • Fred Hutch/University of Washington Cancer Consortium
    • Seattle Washington 98109 United States

    View trial on ClinicalTrials.gov


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    Published December 12, 2016
  • Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"

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    Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"


    Condition: Upper Tract Urothelial Carcinoma

    Intervention:

    • Procedure: RNU
    • Drug: Gemcitabine/Cisplatin
    • Drug: M-VAC Protocol

    Purpose: The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC) treatments based in real world data in various European countries. The study will allow to gain insight in the true proportion of patients that fit to receive complete cisplatin-based neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients with poor prognostic factors (PS and renal function) who receive only standard treatment (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic and treatment protocol.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02969083

    Sponsor: The European Uro-Oncology Group

    Primary Outcome Measures:

    • Measure: Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
    • Time Frame: 6 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Disease Free Survival (DFS)
    • Time Frame: 1-2 years
    • Safety Issue:
    • Measure: Overall Survival (OS)
    • Time Frame: 1-2 years
    • Safety Issue:
    • Measure: Cancer-Specific Survival (CSS)
    • Time Frame: 1-2 years
    • Safety Issue:

    Estimated Enrollment: 200

    Study Start Date: May 28, 2018

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Written informed consent
    • Age > 18 years
    • Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification)
    • Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception
    • Patients without bladder cancer or with concomitant non muscle invasive bladder cancer
    • Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF 55 ml/min: Electrolytes: potassium, magnesium and calcium: within normal limits.
    • CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis Exclusion Criteria:
    • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
    • History of cardiovascular conditions within the past 6 months.
    • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an

    Exclusion Criteria:

    • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
    • History of cardiovascular conditions within the past 6 months.
    • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment.
    • Any major contraindication to a surgical procedure.
    • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
    • Active infection contraindicating chemotherapy
    • Concomitant diseases that are a formal exclusion to platinum-based chemotherapy (deafness, grade II neuropathy).
    • Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, Prostate specific antigen (PSA) <10. Patients with past medical history of cancer can be included if diagnosed at least 5 years ago.
    • Concomitant muscle invasive bladder cancer
    • Patients who have been or still are on methotrexate treatment.

    Contact:

    • Cristina Alvarez, MSc, PhD
    • +31(0)715264109

    Locations:

    • Radboud University Medical Centre
    • Nijmegen Gelderland Netherlands
    • Leiden University Medical Centre
    • Leiden South Holland Netherlands
    • Alrijne Ziekenhuis
    • Leiderdorp South-Holland Netherlands
    • Haukeland University Hospital
    • Bergen Norway
    • Fundacion Puigvert
    • Barcelona Spain
    • Hospital San Pau
    • Barcelona Spain

    View trial on ClinicalTrials.gov


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    Published November 30, 2018
  • Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

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    Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations


    Condition: Cholangiocarcinoma, Brain Tumor, Urothelial Cancer, Other Tumor Types With FGFR2 Gene Fusions, Activating Mutations, FGFR2 Amplification

    Intervention:

    • Drug: TAS-120

    Purpose: This is an open-label, nonrandomized, Phase 1 dose-escalation, dose-expansion, and Phase 2 study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients with advanced solid tumors with and without FGF/FGFR-related abnormalities. The study will be conducted in 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D of TAS-120 in which this part of the study has been completed; (2) Phase 1 expansion to further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas , urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or amplification. Up to approximately 185 patients will be enrolled in the phase 1 expansion; and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02052778

    Sponsor: Taiho Oncology, Inc.

    Primary Outcome Measures:

    • Measure: Phase 1 - Overall Response Rate (ORR)
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Phase 1 - Early Progression Rate (EPR) for GBM or grade III glioma
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Phase 2 - Overall Response Rate (ORR)
    • Time Frame: 12 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Duration of Response (DOR)
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Disease Control Rate (DCR)
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Progression free survival (PFS)
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Patient Reported Outcome (PRO)
    • Time Frame: 12 months
    • Safety Issue:
    • Measure: Overall Survival (OS)
    • Time Frame: 12 months
    • Safety Issue:

    Estimated Enrollment: 371

    Study Start Date: July 2014

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria: Phase 1 Expansion 1. Patient has failed all standard therapies or standard therapy does not exist or is not tolerated. 2. Patient has specific FGF/FGFR aberrations
    • Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or amplifications
    • Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic oligodendroglioma) with FGFR gene fusions or activating mutations.
    • Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
    • All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (≥ 10 copies), FGFR gene fusions, or FGFR activating mutations Phase 2 1. Patient has histologically or cytologically confirmed, locally advanced, metastatic, unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by the Sponsor's designated central laboratory 2. Patient has been treated with and failed at least one prior systemic gemcitabine and platinum-based chemotherapy for the advanced disease 3. Must have documentation of radiographic progression of disease on prior systemic therapy 4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO criteria (2010) for brain tumors. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 6. Adequate organ function

    Exclusion Criteria:

    1. A patient will be excluded from this study if any of the following criteria are met:
    2. History and/or current evidence of non-tumor related alteration of calcium-phosphorus homeostasis.
    3. History and/or current evidence of clinically significant ectopic mineralization/calcification.
    4. History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination.
    5. A serious illness or medical condition(s)

    Contact:

    • Jerry Huang, MD

    Locations:

    • Banner MD Anderson Cancer Center
    • Gilbert Arizona 85234 United States
    • Mayo Clinic (AZ)
    • Scottsdale Arizona 85259 United States
    • City of Hope National Medical Center
    • Duarte California 91010 United States
    • UCSF - Helen Diller
    • San Francisco California 94158 United States
    • Mayo Clinic (Jacksonville)
    • Jacksonville Florida 32224 United States
    • Florida Hospital
    • Orlando Florida 32804 United States
    • Cancer Treatment Centers of America
    • Newnan Georgia 30265 United States
    • Cancer Treatment Centers of America Zion, IL
    • Zion Illinois 60099 United States
    • The University of Kansas Cancer Center
    • Westwood Kansas 66205 United States
    • Massachusetts General Hospital
    • Boston Massachusetts 02114 United States
    • Cancer Center at Beth Israel Deaconess Medical Center
    • Boston Massachusetts 02215 United States
    • Dana Farber Cancer Institution
    • Boston Massachusetts 02215 United States
    • Wayne State Universtity (Karmanos Cancer Institute)
    • Detroit Michigan 48201 United States
    • Mayo Clinic (MN)
    • Rochester Minnesota 55905 United States
    • New Mexico Cancer Care Alliance
    • Albuquerque New Mexico 87106 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • University of Pennsylvania
    • Philadelphia Pennsylvania 19104 United States
    • Sidney Kimmel Cancer Center at Jefferson
    • Philadelphia Pennsylvania 19107 United States
    • Cancer Treatment Centers of America Philadelphia, PA
    • Philadelphia Pennsylvania 19124 United States
    • University of Pittsburgh Medical Center
    • Pittsburgh Pennsylvania 15232 United States
    • Greenville Health System ITOR
    • Greenville South Carolina 29605 United States
    • Spartanburg Medical Center
    • Spartanburg South Carolina 29303 United States
    • Mary Crowley
    • Dallas Texas 75251 United States
    • MD Anderson Cancer Center
    • Houston Texas 77030 United States
    • Virginia Mason Cancer Center
    • Seattle Washington 98101 United States
    • UW Carbone Cancer Center
    • Madison Wisconsin 53792 United States
    • Medical College of Wisconsin
    • Milwaukee Wisconsin 53226 United States
    • Royal Melbourne Hospital
    • Melbourne Australia
    • Scientia Clinical Research University of New South Wales
    • Randwick 2031 Australia
    • Scientia Clinical Research University of New South Wales
    • Randwick NSW 2031 Australia
    • Institut Bergonie
    • Bordeaux 33000 France
    • Hospices Civils de Lyon
    • Bron 69677 France
    • Centre Léon Bérard Bât
    • Lyon 69008 France
    • Pitié-Salpêtrière Hospital
    • Paris 75013 France
    • Institute Goustave-Roussy
    • Paris France
    • Rennes, Centre Eugène Marquis
    • Rennes cedex 35042 France
    • The Chinese University of Hong Kong
    • Sha Tin Hong Kong
    • Prince of Wales Hospital
    • Shatin Hong Kong
    • Nagoya University Hospital
    • Nagoya 466-8560 Japan
    • Osaka International Cancer Institute
    • Osaka 541-8567 Japan
    • Yonsei University, Severance Hospital (Seoul)
    • Seoul 03722 Korea, Republic of
    • ASAN Medical Center (Seoul)
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center (Seoul)
    • Seoul 06351 Korea, Republic of
    • Seoul National University Hospital
    • Seoul 110-744 Korea, Republic of
    • University of Amsterdam
    • Amsterdam 1105AZ Netherlands
    • Val D'Hebron University Hospital
    • Barcelona 08035 Spain
    • Hospital Clinic i Provincial de Barcelona,
    • Barcelona 08036 Spain
    • University Hospital Ramón y Cajal
    • Madrid 28034 Spain
    • Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro
    • Madrid Spain
    • National Taiwan University Hospital
    • Taipei 10048 Taiwan
    • Guy's and St Thomas' NHS Foundation Trust
    • London SE1 9RT United Kingdom
    • University College London Hospital
    • London W1T 7HA United Kingdom
    • Sarah Cannon Research Institute
    • London United Kingdom

    View trial on ClinicalTrials.gov


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    Published July 28, 2019
  • Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Pembrolizumab in Metastatic Urothelial Cancer

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    Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Pembrolizumab in Metastatic Urothelial Cancer


    Condition: Metastatic Urothelial Cancer

    Intervention:

    • Drug: pembrolizumab

    Purpose: The goal of the proposed research project is to assess the safety (dose limiting toxicity, DLT) of the combination of pembrolizumab and high-dose stereotactic body radiotherapy (SBRT) in patients with metastatic urothelial cancer. Both the SBRT dose and pembrolizumab dose will be fixed, but the timing of the combination will be varied. Secondary objectives include response rates, local control, progression-free survival (PFS) and overall survival (OS). Exploratory endpoints include immunologic responses and response rates in PD-L1- TIL- tumors. The combination sequence with the most promising response rates and the best safety profile will be selected to continue in a Phase II trial.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02826564

    Sponsor: University Hospital, Ghent

    Primary Outcome Measures:

    • Measure: Selection of the sequence arm with a DLT < 20% based on the incidence of treatment-related adverse events
    • Time Frame: 12 weeks post-radiotherapy
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Tumor response
    • Time Frame: 12 weeks
    • Safety Issue:
    • Measure: Immunologic response in peripheral blood
    • Time Frame: 12 weeks
    • Safety Issue:

    Estimated Enrollment: 20

    Study Start Date: June 2016

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be ≥ 18 years of age on day of signing informed consent. 3. Have measurable disease based on RECIST 1.1. 4. Have had any prior treatment more than 2 weeks prior to study day 1, treatment naïve patients are allowed 5. Histologically confirmed diagnosis of urothelial carcinoma 6. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. 7. Have a performance status of 0 or 1 on the ECOG Performance Scale. 8. Demonstrate adequate organ function, all screening labs should be performed within 10 days before treatment initiation. (Adequate organ function: Absolute neutrophil count (ANC) ≥1,500 /mcL, Platelets ≥100,000 / mcL, Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment), Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN, Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases, Albumin >2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated per institutional standard) 9. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2
    • Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 11. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    Exclusion Criteria:

    • The subject must be excluded from participating in the trial if the subject: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has had radiotherapy interfering with SBRT. 3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 4. Has a known history of active TB (Bacillus Tuberculosis) 5. Hypersensitivity to pembrolizumab or any of its excipients. 6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 7. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
    • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 8. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 9. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 11. Has known history of, or any evidence of active, non-infectious pneumonitis. 12. Has an active infection requiring systemic therapy. 13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 19. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

    Contact:

    • Piet Ost, PhD

    Location:

    • University Hospital Ghent
    • Ghent 9000 Belgium

    View trial on ClinicalTrials.gov


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    Published July 29, 2017
  • Phase II Open Label Single Arm Exploratory Trial of Oral Afatinib Monotherapy Following Platinum Failure for Patients With Advanced/Metastatic Urothelial Tract Carcinoma With ERBB Receptor Deregulation.

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    LUX-Bladder 1: Phase II Open Label Single Arm Exploratory Trial of Oral Afatinib Monotherapy Following Platinum Failure for Patients With Advanced/Metastatic Urothelial Tract Carcinoma With Genetic Alterations in ERBB Receptors.


    Condition: Urologic Neoplasms

    Intervention:

    • Drug: Afatinib

    Purpose: The purpose of this trial is to assess the anti-tumour activity and safety of afatinib monotherapy in patients with urothelial tract carcinoma carrying ERBB2 or ERBB3 mutations or ERBB2 amplifications (Cohort A), and EGFR amplification positive tumours (Cohort B), progressing despite previous platinum based chemotherapy, and thereby to improve their prognosis. The antitumour activity of afatinib monotherapy in these patients will be assessed by progression free survival rate at 6 months (PFS6). This will be the primary endpoint of the trial. A key secondary endpoint will also be defined, the objective response rate (ORR).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02780687

    Sponsor: Boehringer Ingelheim

    Primary Outcome Measures:

    • Measure: Progression Free Survival at 6 months in Cohort A (defined as the proportion of patients who does not show disease progression by the 24-week tumour assessment).
    • Time Frame: 24 weeks
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Objective response rate (ORR) in Cohort A, defined as number of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1.
    • Time Frame: From Baseline to disease progression (up to 2 years)
    • Safety Issue:
    • Measure: Progression free survival (PFS) in Cohort A, defined as the time from first drug administration to the date of disease progression, or date of death whichever is earlier
    • Time Frame: Starting with first drug administration and until up to 2 years for each patient
    • Safety Issue:
    • Measure: Overall Survival (OS) in Cohort A, defined as the time from first drug administration to the date of death
    • Time Frame: From first drug administration to date of death (up to 5 years)
    • Safety Issue:
    • Measure: Disease Control Rate (DCR) in Cohort A, defined as complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-Progressive Disease (NN) according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1
    • Time Frame: From first drug administration to disease progression (up to 2 years)
    • Safety Issue:
    • Measure: Duration of objective response (DOR) in Cohort A, according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1
    • Time Frame: From first drug administration to disease progression (up to 2 years)
    • Safety Issue:
    • Measure: Tumour shrinkage in Cohort A, measured as the maximum percentage decrease from baseline sum of target lesion diameters after treatment until disease progression
    • Time Frame: From first drug administration to disease progression (up to 2 years)
    • Safety Issue:

    Estimated Enrollment: 80

    Study Start Date: June 9, 2016

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Recurrent or metastatic urothelial cancer
    • Patients must have failed prior platinum based treatment (adjuvant or 1st line)
    • Archival tissue sample available for biomarker testing at pre-screening and tissue banking.
    • Patients should complete a pre-screening biomarker analysis and should fulfill the following: for Cohort A tumour should show a ERBB2 (epidermal growth factor family receptor 2) or ERBB3 mutation, or ERBB2 gene amplification; for Cohort B tumour should show EGFR (Epidermal Growth Factor Receptor) amplification.
    • Further inclusion criteria apply Exclusion criteria:
    • Prior use of EGFR, ERBB2 or ERBB3 targeted treatment
    • Chemotherapy within 4 weeks prior to the start of study treatment. Biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first
    • Known brain metastases or signs hereof, uncontrolled spinal cord compression or leptomeningeal carcinomatosis
    • Further

    Exclusion Criteria:

    • Prior use of EGFR, ERBB2 or ERBB3 targeted treatment
    • Chemotherapy within 4 weeks prior to the start of study treatment. Biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first
    • Known brain metastases or signs hereof, uncontrolled spinal cord compression or leptomeningeal carcinomatosis
    • Further exclusion criteria apply

    Contact:

    • Boehringer Ingelheim Call Center
    • 1-800-243-0127

    Locations:

    • INS Bergonié
    • Bordeaux 33076 France
    • CTR Léon Bérard
    • Lyon 69373 France
    • INS Cancérologie du Gard
    • Nîmes 30029 France
    • HOP Saint-Louis
    • Paris 75010 France
    • HOP Cochin
    • Paris 75014 France
    • HOP Européen G. Pompidou
    • Paris 75015 France
    • HOP Foch
    • Suresnes 92150 France
    • INS Claudius Regaud
    • Toulouse 31059 France
    • INS Gustave Roussy
    • Villejuif 94805 France
    • Ospedale San Donato di Arezzo
    • Arezzo 52100 Italy
    • A.O. San Camillo Forlanini
    • Roma 00152 Italy
    • Hospital Germans Trias i Pujol
    • Badalona 08916 Spain
    • Hospital del Mar
    • Barcelona 08003 Spain
    • Hospital Santa Creu i Sant Pau
    • Barcelona 08025 Spain
    • Hospital Clínic de Barcelona
    • Barcelona 08036 Spain
    • Hospital Vall d'Hebron
    • Barcelona 08038 Spain
    • Hospital Universitario de Elche
    • Elche 03202 Spain
    • Hospital Universitari de Girona Doctor Josep Trueta
    • Girona 17007 Spain
    • Hospital Duran i Reynals
    • L'Hospitalet de Llobregat 08908 Spain
    • Hospital Universitario Lucus Augusti
    • Lugo 27003 Spain
    • Hospital Ramón y Cajal
    • Madrid 28034 Spain
    • Hospital Clínico San Carlos
    • Madrid 28040 Spain
    • Hospital Universitario 12 de Octubre
    • Madrid 28041 Spain
    • Hospital La Paz
    • Madrid 28046 Spain
    • CIO Clara Campal
    • Madrid 28050 Spain
    • Hospital Son Espases
    • Palma de Mallorca 07010 Spain
    • CS Parc Taulí
    • Sabadell 08208 Spain
    • Hospital Virgen Macarena
    • Sevilla 41009 Spain
    • Hospital Virgen del Rocío
    • Sevilla 41013 Spain
    • Instituto Valenciano de Oncología
    • Valencia 46009 Spain

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy

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    Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy


    Condition: Urothelial Carcinoma

    Intervention:

    • Drug: Sacituzumab govitecan

    Purpose: This is an international, multi-center, open-label, phase II study in patients with metastatic urothelial cancer after failure of platinum-based regimen or anti-PD-1 /PD-L1 based immunotherapy. At least 140 patients are anticipated to be enrolled across approximately 70 sites from North America, Europe and Asia.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03547973

    Sponsor: Immunomedics, Inc.

    Primary Outcome Measures:

    • Measure: Overall Response Rate (ORR)
    • Time Frame: 2 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Duration of Response (DOR)
    • Time Frame: 2 years
    • Safety Issue:
    • Measure: Progression-Free Survival (PFS)
    • Time Frame: 2 years
    • Safety Issue:
    • Measure: Overall Survival (OS)
    • Time Frame: 2 years
    • Safety Issue:

    Estimated Enrollment: 140

    Study Start Date: August 31, 2018

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients with histologically confirmed urothelial cancer.
    • ECOG Performance status score of 0 or 1.
    • Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin): 1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease; 2. Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
    • Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an anti-PD-1 /PD-L1 therapy.
    • Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Subject may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
    • Adequate renal and hepatic function.
    • Adequate hematologic parameters without transfusional support.
    • Creatinine clearance ≥30mL/min as calculated by the Cockroft-Gault formula.
    • Subjects must have a 3-month life expectancy.
    • Have measurable disease by CT or MRI as per RECIST 1.1 criteria.

    Exclusion Criteria:

    • Women who are pregnant or lactating.
    • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
    • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
    • Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
    • Has an active second malignancy.
    • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
    • Has known active Hepatitis B or Hepatitis C
    • Has other concurrent medical or psychiatric conditions

    Contact:

    • Allison Gladden
    • 862-260-3506

    Locations:

    • Honor Health Research Institute
    • Avondale Arizona 85323 United States
    • American Institute of Research
    • Tucson Arizona 85712 United States
    • University of Arizona Cancer Center
    • Tucson Arizona 85719 United States
    • University of Southern California Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States
    • American Institute of Research
    • Whittier California 90603 United States
    • Rocky Mountain Cancer Centers- Littleton
    • Littleton Colorado 80120 United States
    • Smilow Cancer Hospital at Yale-New Haven
    • New Haven Connecticut 06510 United States
    • Mount Sinai Medical Center Comprehensive Cancer Center
    • Miami Beach Florida 33140 United States
    • Woodlands Medical Specialists
    • Pensacola Florida 32503 United States
    • University of South Florida H. Lee Moffitt Cancer Center & Research Inst.
    • Tampa Florida 33612 United States
    • Winship Cancer Institute
    • Atlanta Georgia 30322 United States
    • Norton Cancer Institute
    • Louisville Kentucky 40241 United States
    • Maryland Oncology Hematology-Brandywine
    • Brandywine Maryland 20613 United States
    • University of Michigan Comprehensive Medical Center
    • Ann Arbor Michigan 48109 United States
    • Barbara Ann Karmanos Cancer Institute
    • Detroit Michigan 48201 United States
    • University of Mississippi Medical Center
    • Jackson Mississippi 38677 United States
    • Nebraska Cancer Specialists-Midwest Cancer Center-Legacy
    • Omaha Nebraska 68130 United States
    • Urology Cancer Center
    • Omaha Nebraska 68130 United States
    • The Oncology Institute of Hope and Innovation
    • Henderson Nevada 89052 United States
    • Comprehensive Cancer Centers of Nevada
    • Las Vegas Nevada 89134 United States
    • New Mexico Oncology Hematology Consultants/Precision Cancer Research
    • Albuquerque New Mexico 87109 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14203 United States
    • Northwell Health
    • Lake Success New York 11042 United States
    • New York University Langone Medical
    • New York New York 10016 United States
    • Weill Cornell Medicine
    • New York New York 10021 United States
    • Stony Brook Medicine Cancer Care
    • Stony Brook New York 11794 United States
    • Saint Luke's Cancer Center-Anderson Campus
    • Easton Pennsylvania 18045 United States
    • Vanderbilt-Ingram Cancer Center
    • Nashville Tennessee 37232 United States
    • Houston Methodist Hospital
    • Houston Texas 77030 United States
    • Renovatio Clinical Consultants
    • Houston Texas 77056 United States
    • University of Texas Health Science Center at San Antonio
    • San Antonio Texas 78229 United States
    • Huntsman Cancer Hospital
    • Salt Lake City Utah 84112 United States
    • Virginia Oncology Associates
    • Norfolk Virginia 23666 United States
    • Blue Ridge Cancer Care
    • Roanoke Virginia 24014 United States
    • Seattle Cancer Care Alliance at South Lake Union
    • Seattle Washington 98109 United States
    • University of Wisconsin Hospital and Clinics
    • Madison Wisconsin 53705 United States
    • Universitair Ziekenhuis Antwerpen
    • Edegem Antwerpen 2650 Belgium
    • Institut Jules Bordet
    • Bruxelles Brussels 1070 Belgium
    • Grand Hopital de Charleroi-Notre Dame
    • Charleroi Hainaut 6000 Belgium
    • Ziekenhuis Netwerk Antwerpen Middelheim
    • Antwerpen 2020 Belgium
    • Thomayerova Nemocnice
    • Prague Praha 140 59 Czechia
    • Fakultni' Nemocnice Na Bulovce
    • Prague Praha 180 00 Czechia
    • Fakultni' Nemocnice Ostrava
    • Ostrava Severomoravsky Kraj 708 52 Czechia
    • Fakultni' Nemocnice Olomouc
    • Olomouc 779 00 Czechia
    • Les Hopitaux Uiversitaires de Strasbourg
    • Strasbourg Cedex Alsace 67097 France
    • Gustave Roussy
    • Villejuif Ile -de-France 94800 France
    • Institut Curie
    • Paris Cedex 05 Ile-de-France 75248 France
    • Institut Clausius Re'gaud
    • Paris Ile-de-France 75010 France
    • Assistance Publique-Hopitaux de Paris Hopital Cochin
    • Paris Ile-de-France 75014 France
    • Hopital Foch
    • Suresnes Ile-de-France 92150 France
    • Centre Le'on Be'rard
    • Lyon Cedex 08 Rhone-Alpes 69373 France
    • National Cancer Center
    • Goyang-si Gyeonggi-Do 10408 Korea, Republic of
    • The Catholic University of Korea St. Vincent's Hospital
    • Suwon-si Gyeonggi-Do 16247 Korea, Republic of
    • Pusan National University Yangsan Hospital
    • Yangsan Gyeongsangnam-Do 626-770 Korea, Republic of
    • Seoul National University Hospital
    • Seoul 030380 Korea, Republic of
    • Severance Hospital
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 06351 Korea, Republic of

    View trial on ClinicalTrials.gov


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    Published February 16, 2019
  • Phase II Trial of Gemcitabine-Eribulin (GE) in Cisplatin Ineligible Patients With Advanced or Unresectable Urothelial Carcinoma of the Bladder

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    Phase II Trial of Gemcitabine-Eribulin (GE) in Cisplatin Ineligible Patients With Advanced or Unresectable Urothelial Carcinoma of the Bladder


    Condition: Metastatic Ureteral Neoplasm, Metastatic Urethral Neoplasm, Stage III Bladder Urothelial Carcinoma, Stage III Ureter Cancer, Stage III Urethral Cancer, Stage IV Bladder Urothelial Carcinoma, Stage IV Ureter Cancer, Stage IV Urethral Cancer, Ureter Urothelial Carcinoma, Urethral Urothelial Carcinoma

    Intervention:

    • Drug: Eribulin Mesylate
    • Drug: Gemcitabine Hydrochloride

    Purpose: This phase II trial studies how well gemcitabine hydrochloride and eribulin mesylate work in treating patients with bladder cancer that has spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02178241

    Sponsor: National Cancer Institute (NCI)

    Primary Outcome Measures:

    • Measure: Objective response rate defined as either a confirmed complete response (CR) or a confirmed partial response (PR) based on RECIST version 1.1
    • Time Frame: Up to 36 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Incidence of adverse events as graded by the CTCAE v. 4
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Overall response rate (ORR)
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: Up to 36 months
    • Safety Issue:
    • Measure: PFS using RECIST v1.1
    • Time Frame: From the start of treatment on day 1, until progression, death, or the start of another treatment, assessed up to 12 months
    • Safety Issue:

    Estimated Enrollment: 21

    Study Start Date: December 2014

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment
    • Patients must have histologically confirmed predominantly urothelial carcinoma of the bladder, ureter, or urethra
    • Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
    • Patients must be ineligible for treatment with cisplatin, based on one of:
    • Calculated creatinine clearance (CrCl) >= 30 and < 60 mL/min (Cockcroft-Gault)
    • CTCAE grade (Gr) >= 2 hearing loss
    • CTCAE Gr >= 2 neuropathy
    • Patients must not have received prior systemic therapy for their advanced cancer; prior intravesical therapy completed 4 weeks prior to enrollment and adjuvant/neoadjuvant chemotherapy completed more than 6 months prior to diagnosis of advanced disease are permitted
    • Zubrod performance status =< 2 (Karnofsky >= 60%)
    • Life expectancy of greater than 3 months
    • Leukocytes >= 3,000/mcL
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • Total bilirubin < 1.5 times the upper limit of normal (x ULN) for the institution
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
    • Creatinine clearance; calculated creatinine clearance (CrCl) >= 30 mL/min and < 60 mL/min (Cockroft-Gault) unless the patient qualified based on hearing loss or neuropathy
    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of gemcitabine and eribulin administration
    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Patients with a small cell component in their histology are excluded
    • Patients who have had chemotherapy for the treatment of the advanced or unresectable urothelial cancer of the bladder are not eligible; patients who were previously treated for local disease must not have received radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have received neoadjuvant or adjuvant chemotherapy must have completed treatment at least 6 months prior to diagnosis of metastatic disease
    • Patients who are receiving any other investigational agents
    • Patients with known brain metastases should be excluded from this clinical trial
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine and eribulin
    • Uncontrolled intercurrent illness including, but not limited to, a second cancer diagnosis within the past 5 years, or a cancer undergoing any treatment, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
    • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with eribulin and gemcitabine
    • Human immunodeficiency virus (HIV)-positive patients with inadequate cluster of differentiation (CD)4 counts or those who are on combination antiretroviral therapy with strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) effects are ineligible for this trial
    • Patients with baseline corrected QT (QTc) prolongation greater than grade 1 are excluded from this study; patients with grade 1 QTc elevation are eligible but must be monitored with electrocardiogram (ECG) (EKG) exams, for the first 3 cycles of treatment; eribulin time to maximum concentration (Cmax) after infusion is about 10 minutes, and half life is 40 minutes; ECG (EKG) should be performed between 10 to 40 minutes after eribulin administration (on day 1 and day 8 of treatment); continued ECG (EKG) monitoring beyond cycle 3 can be done at the discretion of the treating physician
    • Patients with congenital long QT syndrome are excluded from this study
    • Other medications known to prolong QT interval should be discontinued and if not possible, patient is excluded from this study

    Locations:

    • City of Hope Comprehensive Cancer Center
    • Duarte California 91010 United States
    • Los Angeles County-USC Medical Center
    • Los Angeles California 90033 United States
    • USC / Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States
    • Keck Medical Center of USC Pasadena
    • Pasadena California 91105 United States
    • University of California Davis Comprehensive Cancer Center
    • Sacramento California 95817 United States
    • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora Colorado 80045 United States
    • MedStar Georgetown University Hospital
    • Washington District of Columbia 20007 United States
    • Moffitt Cancer Center P2C
    • Tampa Florida 33612 United States
    • University of Chicago Comprehensive Cancer Center
    • Chicago Illinois 60637 United States
    • UC Comprehensive Cancer Center at Silver Cross
    • New Lenox Illinois 60451 United States
    • Mayo Clinic Cancer Center P2C
    • Rochester Minnesota 55905 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • Case Western Reserve University
    • Cleveland Ohio 44106 United States
    • Cleveland Clinic Foundation
    • Cleveland Ohio 44195 United States
    • Ohio State University Comprehensive Cancer Center
    • Columbus Ohio 43210 United States
    • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh Pennsylvania 15232 United States
    • University of Texas M D Anderson Cancer Center P2C
    • Houston Texas 77030 United States
    • University Health Network Princess Margaret Cancer Center P2C
    • Toronto Ontario M5G 2M9 Canada

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy

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    Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy


    Condition: Metastatic Urothelial Carcinoma (UC)

    Intervention:

    • Drug: Palbociclib

    Purpose: This multicenter phase II trial will evaluate palbociclib (PD-0332991) in patients with metastatic urothelial carcinoma (UC) with cyclin-dependent kinase inhibitor 2A (CDKN2A) (also referred to as p16) loss and positive Retinoblastoma (Rb) expression after failure of first-line chemotherapy.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02334527

    Sponsor: UNC Lineberger Comprehensive Cancer Center

    Primary Outcome Measures:

    • Measure: Progression Free Survival
    • Time Frame: 4 Months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Progression Free Survival (PFS) and Overall Survival (OS)
    • Time Frame: 4 Months
    • Safety Issue:
    • Measure: Response Rate (RR)
    • Time Frame: 4 Months
    • Safety Issue:
    • Measure: Number of participants with adverse events
    • Time Frame: 30 Days
    • Safety Issue:

    Estimated Enrollment: 40

    Study Start Date: March 2015

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Age ≥ 18 years
    • ECOG Performance status of ≤ 2 (see section 11.1, Appendix A)
    • Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis with Rb+/CDKN2A- based on immunohistochemistry (IHC) of tissue blocks or unstained slides performed within a CLIA-certified laboratory at UNC; if stage I of original cohort indicates futility, molecular requirement for eligibility will change to Rb+/CCND1 overexpression (also based on IHC); see statistical section, section 8.0)
    • Metastatic disease that is not amenable to curative surgery or radiation
    • Prior treatment with ≤ two prior cytotoxic regimens; prior therapy must have consisted of at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel or gemcitabine. If the only prior cytotoxic therapy was administered in the perioperative i.e. neoadjuvant or adjuvant settings, patient is eligible provided the interval from end of therapy to the diagnosis of metastatic disease is less than one year.
    • Progressive disease during or after treatment with at least one of the agents listed above
    • At least one measurable disease site (as defined by RECIST1.1) that has not been previously irradiated
    • No prior therapy with a CDK 4/6 inhibitor; prior anti PD1 and anti PD-L1 therapy is permitted
    • Washout period should be at least 2 weeks for prior chemotherapy or radiation therapy 3.1.10 Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, surgery to ≤ grade 1 per NCI CTCAEv4 except neuropathy which may be ≤ grade 2
    • No active brain metastases
    • Adequate bone marrow, liver and renal functions as assessed by the following:
    • Hemoglobin ≥ 8 g/dL;
    • Absolute neutrophil count ≥ 1,500/uL;
    • Platelets ≥ 75,000 g/uL;
    • Total bilirubin ≤ 1.5 times upper limit of normal (ULN);
    • ALT and AST ≤ 2.5 times ULN;
    • serum creatinine ≤ 2.5 times ULN;
    • Negative serum pregnancy test in women of child-bearing potential within 7 days of D1 of treatment
    • If fertile, agree to use effective contraception (condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during trial
    • Life expectancy greater than 3 months
    • Subject must be able to give written IRB approved informed consent and be able to follow protocol requirements

    Exclusion Criteria:

    • Any prior treatment with any investigational drug within the preceding 4 weeks
    • Any concurrent active malignancy requiring treatment (other than basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, other malignancies curatively treated > 3 years prior to study entry) or patients with adenocarcinoma of the prostate that has been surgically treated and with a post-treatment PSA that is non-detectable.
    • Unstable systemic disease or active uncontrolled infection
    • Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to study entry
    • Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study due to potential CYP3A4 interaction with the study medication. Orange juice is allowed.
    • Intake of any herbal preparations or medications (including, but not limited to, Saint John's Wort and ginkgo biloba) and dietary supplements within 7 days prior to first dose of study drug
    • Unable or unwilling to discontinue use of any drug known to be a strong or moderate inhibitor or inducer of CYP3A4 (prohibited inducers and inhibitors must be discontinued within 2 weeks prior to first dose of study drug; see section 11.2 Appendix B); unable or unwilling to discontinue use of any proton pump inhibitor; see section 11.2, Appendix B
    • Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug
    • Inability to swallow oral medications
    • Pregnant or breast-feeding
    • Substance abuse, or medical, psychological or social conditions that may interfere with the patient's participation in the study or the evaluation of the study results
    • Other serious, ongoing, non-malignant disease or infection that would compromise protocol objectives

    Contact:

    • Maureen Tynan, RN
    • 919-843-7039

    Locations:

    • University of Michigan
    • Ann Arbor Michigan 48109 United States
    • North Carolina Cancer Hospital (UNC)
    • Chapel Hill North Carolina 27599 United States
    • Vanderbilt-Ingram Cancer Center
    • Nashville Tennessee 37232 United States

    View trial on ClinicalTrials.gov


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    Published July 29, 2017
  • Prophylactic Cranial Irradiation (PCI) for Patients With Small Cell Carcinoma of the Urothelium

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    Prophylactic Cranial Irradiation (PCI) for Patients With Small Cell Carcinoma of the Urothelium


    Condition: Bladder Cancer

    Intervention:

    • Radiation: Prophylactic Cranial Irradiation (PCI)
    • Other: Brain X-ray

    Purpose: The goal of this clinical research study is to learn if whole brain radiation can lower the chances of developing brain tumors in patients with small cell carcinoma of the urinary tract, including the bladder. The safety of whole brain radiation will also be studied.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT00756639

    Sponsor: M.D. Anderson Cancer Center

    Primary Outcome Measures:

    • Measure: Brain Metastasis Free Survival
    • Time Frame: At 1 Year
    • Safety Issue:

    Estimated Enrollment: 30

    Study Start Date: June 2008

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Patients with histologically proven small cell carcinoma of the bladder, or elsewhere along the urothelium, which is locally advanced or metastatic (i.e. > or = cT3b, > or = pT3b, N+, or M+) at the time of presentation or cystectomy who have been treated with chemotherapy.
    2. Patients must have had a response to chemotherapy, which the investigator feels is likely to resulting systemic control of the cancer. In most instances, this would reflect a major response (i.e. > or = 90% reduction of tumor), though a lower percentage may be acceptable if the investigator feels the residual reflects another component, such as transitional cell carcinoma (TCC). Dr Arlene Siefker-Radtke will serve as the final arbiter when questions regarding response arise.
    3. Since small cell tumors of the bladder are often associated with other variant histology including TCC and adenocarcinoma, the presence of variant histology will be allowed.
    4. Patients must be > or = 18 years of age.
    5. Patients may be on other trials (either here at M.D. Anderson Cancer Center or at an outside institution) as long as the other

    Eligibility Criteria:

    1. are met.
    2. Patients must not have any evidence of progressive disease at the time of study entry.
    3. Patients must have an MRI or CT of the head showing no CNS metastases within 6 weeks of study entry.
    4. Patients must have adequate physiologic reserves as evidenced by: a) Zubrod Performance Status (PS) of < or = 2; b) Adequate bone marrow reserves as evidenced by ANC > 1000, and platelet count > 75,0
    5. Supranormal values judged to be of benign or inconsequential etiology will be acceptable.
    6. Patients must be enrolled within 6 months of completing chemotherapy or after surgery of the primary site. Any acute/subacute > or = grade 3 toxicities from the chemotherapy must be resolved to < or = grade 2 at the time of study entry. It is suggested that patients undergo prophylactic cranial irradiation as a soon as they have recovered from chemotherapy or surgery, at a minimum of 2 weeks, and up to 6 months following chemotherapy or surgery.

    Exclusion Criteria:

    1. Patients with CNS metastasis at presentation will not be eligible.
    2. History of TIA or stroke within 6 months of study entry.
    3. Prior cranial irradiation.
    4. Pregnant women will not be eligible; women of childbearing potential must have a negative pregnancy test before starting therapy.

    Contact:

    • Seungtaek Choi, MD
    • 713-563-8617

    Location:

    • University of Texas MD Anderson Cancer Center
    • Houston Texas 77030 United States

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
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