Metastatic Urothelial Carcinoma (mUC) Or Advanced Bladder Cancer Articles

Articles

  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02501096

    Sponsor: Eisai Inc.

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01963052

    Sponsor: Astellas Pharma Global Development, Inc.

    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 Cockcroft 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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02091999

    Sponsor: Astellas Pharma Global Development, Inc.

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03330561

    Sponsor: Pieris Pharmaceuticals, Inc.

    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.

    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)

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02318277

    Sponsor: Incyte Corporation

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03288545

    Sponsor: Astellas Pharma Global Development, Inc.

    Phase: Phase 1/Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • Locally advanced or metastatic urothelial cancer (la/mUC)
    • Cohorts A, B, D, E, F, G and K
    • 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
    • Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
    • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
    • 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.
    • Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
    • Muscle Invasive Bladder Cancer (MIBC)- Cohorts H and J
    • Histologically confirmed muscle invasive bladder cancer 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.
    • Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
    • Cohort H and J: Ineligible for cisplatin-based chemotherapy and no prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-muscle invasive bladder cancer.
    • Cohort J: Eligible for pembrolizumab.

    Exclusion Criteria:

    • la/mUC
    • Cohorts A, B, D, E, F, G, and K
    • 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.
    • MIBC
    • Cohorts H and J
    • Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder 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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03170960

    Sponsor: Exelixis

    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 (>10 mg daily prednisone equivalent) 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.

    View trial on ClinicalTrials.gov


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    Published July 28, 2019
  • A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Adva

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    A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Advanced Urothelial Carcinoma


    Condition: Bladder Cancer, Urothelial Carcinoma, Solid Tumor, Advanced Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03980041

    Sponsor: Infinity Pharmaceuticals, Inc.

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
    • Measurable disease by CT or MRI as defined by RECIST v1.1
    • Disease progression or recurrence after treatment:
    • i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
    • ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
    • Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
    • Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
    • Blood sample must be provided for mMDSC levels for randomization into the study

    Exclusion Criteria:

    • Active brain metastases or leptomeningeal metastases
    • Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
    • Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
    • Active, known, or suspected autoimmune disease
    • A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
    • Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
    • Prior surgery or gastrointestinal dysfunction that may affect drug absorption
    • Past medical history of interstitial lung disease
    • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
    • Positive test for hepatitis B, C or HIV
    • Dependent on continuous supplemental oxygen

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03785925

    Sponsor: Nektar Therapeutics

    Phase: Phase 2

    Eligibility:

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

    Key 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

    Key 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 Additional protocol-defined inclusion/

    Exclusion Criteria:

    1. will apply

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02365597

    Sponsor: Janssen Research & Development, LLC

    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. Participants 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 participants will be referred to as chemo-refractory participants. (Participants 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)

    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)

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03374488

    Sponsor: Incyte Corporation

    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.

    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)

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03361865

    Sponsor: Incyte Corporation

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02632409

    Sponsor: Bristol-Myers Squibb

    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

    View trial on ClinicalTrials.gov


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    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

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    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02603432

    Sponsor: Pfizer

    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.

    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

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    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03036098

    Sponsor: Bristol-Myers Squibb

    Phase: Phase 3

    Eligibility:

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

    Inclusion Criteria:

    • Histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer (TCC) of the urothelium involving the renal pelvis, ureter, bladder or urethra
    • No prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer (UC)
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
    • Women and men must agree to follow specific methods of contraception, if applicable Exclusion Criteria:
    • Disease that is suitable for local therapy administered with curative intent
    • Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results
    • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/

    Exclusion Criteria:

    • Disease that is suitable for local therapy administered with curative intent
    • Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results
    • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/exclusion criteria apply

    View trial on ClinicalTrials.gov


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    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

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    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02426125

    Sponsor: Eli Lilly and Company

    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 Programmed death 1 (PD-1), Programmed death-ligand 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.

    View trial on ClinicalTrials.gov


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    Published October 13, 2018
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01772004

    Sponsor: EMD Serono

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02300610

    Sponsor: H. Lee Moffitt Cancer Center and Research Institute

    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)

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-based Treatment Combinations in Patients With Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Co

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    A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-based Treatment Combinations in Patients With Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy (MORPHEUS-mUC)


    Condition: Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03869190

    Sponsor: Hoffmann-La Roche

    Phase: Phase 1/Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • Histologically documented, locally advanced or metastatic UC (also termed TCC or urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
    • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing
    • Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
    • ECOG Performance Status of 0 or 1
    • Measurable disease (at least one target lesion) according to RECIST v1.1
    • Adequate hematologic and end-organ function
    • Negative HIV test at screening
    • Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV) antibody at screening
    • Tumor accessible for biopsy
    • For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs
    • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm Exclusion Criteria:
    • Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
    • Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents
    • Treatment with investigational therapy within 28 days prior to initiation of study treatment
    • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
    • Eligibility only for the control arm
    • Prior allogeneic stem cell or solid organ transplantation
    • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
    • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
    • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
    • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
    • Uncontrolled tumor-related pain
    • Uncontrolled or symptomatic hypercalcemia
    • Symptomatic, untreated, or actively progressing CNS metastases
    • History of leptomeningeal disease
    • Active or history of autoimmune disease or immune deficiency
    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
    • History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
    • Active tuberculosis
    • Severe infection within 4 weeks prior to initiation of study treatment
    • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
    • Significant cardiovascular disease
    • Uncontrolled hypertension
    • Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
    • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
    • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
    • Additional drug-specific

    Exclusion Criteria:

    • Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
    • Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents
    • Treatment with investigational therapy within 28 days prior to initiation of study treatment
    • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
    • Eligibility only for the control arm
    • Prior allogeneic stem cell or solid organ transplantation
    • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
    • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
    • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
    • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
    • Uncontrolled tumor-related pain
    • Uncontrolled or symptomatic hypercalcemia
    • Symptomatic, untreated, or actively progressing CNS metastases
    • History of leptomeningeal disease
    • Active or history of autoimmune disease or immune deficiency
    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
    • History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
    • Active tuberculosis
    • Severe infection within 4 weeks prior to initiation of study treatment
    • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
    • Significant cardiovascular disease
    • Uncontrolled hypertension
    • Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
    • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
    • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
    • Additional drug-specific exclusion criteria might apply

    View trial on ClinicalTrials.gov


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    Published February 7, 2020
  • A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma

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    A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma


    Condition: Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04322643

    Sponsor: Case Comprehensive Cancer Center

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • Men and women ≥ 18 years of age.
    • Histological confirmation of urothelial carcinoma (any histology)
    • Advanced or metastatic urothelial carcinoma.
    • Measurable disease as defined by RECIST 1.1 criteria
    • Has received at least 24 weeks (+/- 4 weeks) on CPI therapy per standard of care (SOC) for advanced urothelial carcinoma
    • Karnofsky Performance Score (KPS) ≥70% (for more information on KPS, please see: http://www.npcrc.org/files/news/karnofsky_performance_scale.pdf)
    • Willing and able to provide informed consent.
    • Laboratory criteria for study entry must meet the following criteria:
    • Serum creatinine ≤ 2 x ULN OR CrCl ≥ 30 mL/min (measured or calculated using the Cockcroft-Gault formula).
    • Hb ≥ 8.0g/dL
    • AST and ALT ≤ 3.0 x ULN
    • Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)

    Exclusion Criteria:

    • History of severe hypersensitivity reaction to any monoclonal antibody.
    • Patients are excluded if they have known HIV/AIDS.
    • Major surgery (eg, cystectomy) less than 28 days prior to the first dose of study drug.
    • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
    • Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
    • Pregnant women are excluded from this study because animal studies have demonstrated that PD-1/PD-L1 inhibitors can cause fetal harm when administered to pregnant women. Breastfeeding women are excluded from this study because PD-1/PD-L1 inhibitors may be excreted in human milk and the potential for serious adverse reactions in nursing infants.

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02717156

    Sponsor: University of Southern California

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02853305

    Sponsor: Merck Sharp & Dohme Corp.

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03682068

    Sponsor: AstraZeneca

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum 130 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

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02812420

    Sponsor: M.D. Anderson Cancer Center

    Phase: Early 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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02412670

    Sponsor: ECOG-ACRIN Cancer Research Group

    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

    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

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT03788746

    Sponsor: AstraZeneca

    Phase:

    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

    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: Advanced Bladder Urothelial Carcinoma, Advanced Ureter Urothelial Carcinoma, 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, Unresectable Bladder Urothelial Carcinoma, Unresectable Renal Pelvis Urothelial Carcinoma, Unresectable Ureter Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03513952

    Sponsor: National Cancer Institute (NCI)

    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 must 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 x institutional upper limit of normal (ULN) (however, patients with known Gilbert's disease who have serum bilirubin level =< 3 x ULN may be enrolled)
    • Aspartate aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (AST and/or ALT=< 5 x ULN for patients with liver involvement)
    • Alkaline phosphatase =< 2.5 x 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 x 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;
    • Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; CYT107 has not been tested for reproductive toxicity yet and may expose to the same risk; 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

    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 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 if patient relapsed >= 12 months later and received additional platinum-based chemotherapy for metastatic disease
    • 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 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
    • Note: Patients with CNS metastases enrolled on trial must also have a brain MRI imaging at all standard radiologic evaluation timepoints
    • 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

    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)

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03260894

    Sponsor: Incyte Corporation

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03219333

    Sponsor: Astellas Pharma Global Development, Inc.

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03473756

    Sponsor: Bayer

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02535650

    Sponsor: Samsung Medical Center

    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 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. Subject has a tumor that carries a missense HRAS mutation according to a standard methodology using Illumina HiSeqTM. (missence non-synonymous HRAS mutation and/or STK11: rs2075606 (T>C))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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03047213

    Sponsor: National Cancer Institute (NCI)

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02736266

    Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

    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.

    View trial on ClinicalTrials.gov


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    Published October 16, 2017
  • An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Locally Advanced and Metastatic Urothelial Carcinoma

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    An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Locally Advanced and Metastatic Urothelial Carcinoma


    Condition: Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03676946

    Sponsor: Lee's Pharmaceutical Limited

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum 75 Years
    • Gender: All

    Inclusion Criteria:

    1. The subject voluntarily gives written informed consent to participate in the study.
    2. Female and male patients aged between 18 and 75 (inclusive).
    3. Subjects must have a histologically and/or cytologically confirmed diagnosis of urothelial carcinoma and the recurrence or metastasis is confirmed again after recurrence, and must have failed or are intolerable to standard therapies or for whom no standard therapies exist.
    4. Must have measurable disease with at least 1 unidimensional measurable lesion (recorded as the maximum diameter) based on RECIST 1.
    5. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1, with estimated life expectancy of at least 3 months.
    6. Adequate blood routine, hepatic and renal function: 1)neutrophil count (ANC) absolutely acuity≥1.5 x 109 / L; 2)platelet count≥80 x 109 / L ; 3)hemoglobin≥90 g/L; 4)serum albumin≥28 g/L; 5)bilirubin≤1.5 x ULN (upper limit of normal ); 6)ALT and AST≤1.5 x ULN, such as liver metastasis, ALT (alanine transaminase) and AST≤5 x ULN; 7)serum Cr≤1.25 x ULN or endogenous creatinine clearance≥50 ml/min (according Cockcroft Gault formula). 7.Female patients of reproductive age should take effective contraception during the study period and within 3 months after the study treatment period. The serum or urine human chorionic gonadotropin (HCG) examination must be negative within 7 days before the study was enrolled.

    Exclusion Criteria:

    1. Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, and still need medical intervention in adult; Patients need bronchodilators for medical intervention of asthma.
    2. Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses >10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
    3. Have received any form of organ transplantation, including allogeneic stem cell transplantation.
    4. Known allergy to macromolecular protein inhibitors or any of the components of ZKAB0
    5. Suffering from other malignant tumors other than this diseases in 5 years except skin basal cell and squamous cell carcinoma or cervical carcinoma in situ.
    6. Central nervous system metastases with clinical symptoms (such as cerebral edema and brain metastases requiring corticosteroid intervention). Previous treatment with brain or meningeal metastasis, such as clinical stabilization (MRI) less than 2 months, or systemic corticosteroid (dose >10mg/day prednisone or equivalent) less than 2 weeks.
    7. Patients with clinical symptoms or heart diseases that cannot be well controlled, such as heart failure above New York Heart Association (NYHA) 2 grade, unstable angina pectoris, myocardial infarction in 1 year, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, left ventricular ejection fraction < 50% at rest as shown in the ultrasound cardiogram.
    8. Patients who had received radiotherapy, chemotherapy, surgery or molecular targeted therapy before, were given less than 4 weeks or 5 half-life (longer time) after the treatment (if treated with nitrosourea or mitomycin previously, the time interval between the end of chemotherapy and study inclusion was less than 6 weeks); Adverse events caused by previous treatment did not recover to level 1 of CTCAE, except for hair loss.
    9. Active infection, or unexplained fever> 38.5 degrees during screening period or before the first dose of ZKAB001 (subjects with fever from the tumor could be enrolled upon investigator's decision).
    10. Human immunodeficiency virus (HIV) positive, syphilis spirochete positive, untreated active hepatitis.
    11. The patient is participating in other clinical studies or is less than 1 month away from the end of the previous clinical study.
    12. Patients may need to receive other systemic cancer treatment during study period.
    13. Prior therapy with an anti-PD 1, anti-PD L1, or anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) antibody (or any other agents that target immunoregulatory receptor).
    14. Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus (HPV) vaccine) within 28 days before screening.
    15. History of mental drug abuse, alcohol abuse or drug abuse.
    16. Pregnant or lactating women.
    17. Any mental condition that prevents the understanding or provision of an informed consent.
    18. It is determined by the investigator that the patient has other factors that may lead to the termination of the study, such as other serious diseases or serious laboratory test abnormalities or other factors that may affect the safety of the subjects, family or social factors that may affect the study data and sample collection.

    View trial on ClinicalTrials.gov


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    Published February 5, 2020
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03070990

    Sponsor: Astellas Pharma Inc

    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.

    View trial on ClinicalTrials.gov


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    Published November 13, 2019
  • Cabozantinib Plus Durvalumab in Patients With Advanced and Chemotherapy-treated Bladder Carcinoma, of Urothelial and Non-urothelial Histology: an Open-label, Single-centre, Phase 2, Single-arm Proof-of-concept Trial: ARCADIA Study

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    Cabozantinib Plus Durvalumab in Patients With Advanced and Chemotherapy-treated Bladder Carcinoma, of Urothelial and Non-urothelial Histology: an Open-label, Single-centre, Phase 2, Single-arm Proof-of-concept Trial: ARCADIA Study


    Condition: Bladder Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03824691

    Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum 90 Years
    • Gender: All

    Inclusion Criteria:

    • Written informed consent.
    • Age ≥18 years.
    • Body weight >30kg
    • Histologically-confirmed diagnosis of UC or variant histologies (e.g. squamous cell carcinoma, adenocarcinoma, micropapillary tumors, BUT excluding pure small cell carcinoma) of the bladder or the urothelium.
    • Either bladder, urethral, or upper tract primary tumor will be allowed.
    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
    • Life expectancy of at ≥ 12 weeks.
    • Availability of tumor tissue for PD-L1 IHC assay.
    • Measurable and non-measurable disease will be included (e.g. patients with bone metastases only will be allowed for inclusion).
    • Failure of 1 or 2 cisplatin-based conventional chemotherapy regimens for metastatic disease (2nd-to-3rd line only).
    • Neoadjuvant/adjuvant regimens will be counted provided that a relapse occurred with 6 months of the last cycle of chemotherapy.
    • Adequate function of the organs: 1. Absolute neutrophil count (ANC) ≥ 1500/mm3 2. Platelets ≥ 100,000/mm3 3. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal. 5. Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL g. Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min using the Cockroft-Gault equation h. Lipase < 2.0 times the upper limit of normal (ULN)
    • Recovery to baseline or ≤ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
    • Ability to swallow tablets
    • Contraception for sexually active fertile patients and their partners. Of note, a barrier method is recommended in addition to the use of steroid hormonal contraceptives, because the effects of cabozantinib on the pharmacokinetics of the latter are unknown.
    • Evidence of post menopausal status or serum pregnancy test for female pre-menopausal subject

    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.
    • Malignancies other than bladder carcinoma 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 significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results.
    • Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments.
    • Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: 1. Evaluable or measurable disease outside the CNS 2. No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) 3. No history of intracranial or spinal cord hemorrhage 4. No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed 5. No evidence of significant vasogenic edema 6. No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 7. Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study 8. Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or surgical resection and ≥ 2 weeks since discontinuation of corticosteroids
    • 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.
    • Clinically significant cardiovascular disease, for example, myocardial infarction (within 3months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication (beta-blockers and digoxin are allowed)
    • Uncontrolled hypertension, stroke or other ischemic or thromboembolic event (DVT, PE) within 6 months before first dose of cabozantinib.
    • 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 enrolmentor anticipation of need for a major surgical procedure during the course of the study other than for diagnosis. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before inclusion. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
    • Received therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to enrolment (patients receiving prophylactic antibiotics, e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease, are eligible).
    • Concomitant anticoagulation with oral anticoagulants or platelet inhibitors.
    • 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 (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
    • radiation therapy for bone within 2 weeks or other radiation therapy within 4 weeks before first dose of study treatment. patients with clinically relevant ongoing complications from prior radiation therapy
    • serious non healing wound/ulcer/bone fracture, moderate to severe hepatic impairment (Child Pugh B or C)
    • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
    • Patients with tumors invading major pulmonary vessels and/or with cavitating pulmonary lesions.
    • Positive test for HIV.
    • Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBs Ag test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
    • Patients with active tuberculosis.
    • Gastrointestinal disorders likely to interfere with absorption of the study drug (e.g. partial bowel obstruction or malabsorption).
    • Subjects with gastrointestinal disorders associated with a high risk of perforation or fistula formation
    • Subjects with active peptic ulcer or with a history of clinically significant GI bleeding within 12 weeks before the first dose of study treatment
    • Prior treatment with CD137 agonists, anti-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.
    • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
    • Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma (PemCab)

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    Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma (PemCab)


    Condition: Metastatic Urothelial Carcinoma, Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03534804

    Sponsor: University of Utah

    Phase: Phase 2

    Eligibility:

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

    Eligibility Criteria:

    1. for consideration of treatment with immunotherapy using a checkpoint inhibitor following surgical resection. Treatment

    Inclusion Criteria:

    • Histologically proven transitional cell or urothelial carcinoma.
    • The following qualifications for patients with locally advanced or metastatic urothelial carcinoma:
    • Patients who are not eligible for cisplatin-containing chemotherapy AND whose tumors express PD-L1 (Combined Positive Score (CPS) ≥ 10 as determined by an FDA-approved test;
    • Patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status;
    • Patients who have disease progression during or following platinum-containing chemotherapy;
    • Patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum- containing therapy.
    • Metastatic (any N+ or M1) or locally advanced, unresectable (T4bN0) disease.
    • Measurable disease is required as determined by RECIST v1.1.
    • Performance Status ECOG 0-2
    • Cisplatin-ineligibility based on ≥1 of the following:
    • Estimated creatinine clearance between ≥30 and <60 ml/min (Cockcroft-Gault formula)
    • ECOG PS>1
    • Hearing loss
    • Baseline neuropathy > grade 1.
    • Patient refusal
    • Be greater to or equal to 18 years of age on day of signing informed consent.
    • Adequate organ function as defined in the protocol
    • Serum albumin ≥ 2.8 g/dl
    • Alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN). ALP ≤ 5 × ULN with documented bone metastases.
    • Negative serum or urine pregnancy test at screening for women of childbearing potential.
    • Highly effective contraception for both male and female subjects throughout the study and for at least 120 days after last pembrolizumab treatment administration if the risk of conception exists.
    • Must have recovered from adverse effects of any prior surgery, radiotherapy or other antineoplastic therapy to grade ≤ 2. If notrecovered to grade ≤ 2, these must be deemed to be irreversible adverse events related to prior surgery and/or radiation therapy (such as incontinence or sexual dysfunction) per investigator clinical judgment.
    • Recovery to baseline or ≤ Grade 2 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. Alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
    • Last dose of any radiation therapy > 2 weeks before first dose of study treatment.
    • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

    Exclusion Criteria:

    • No prior chemotherapy for metastatic urothelial carcinoma, and prior chemotherapy for localized urothelial carcinoma must have been greater than 6 months before registration.
    • Variant histologies other than urothelial carcinoma will not be allowed. Patients with a component of variant histologies will be allowed to enroll, if urothelial carcinoma is the predominant histology. Patients with any component of small cell will be excluded.
    • Has received prior treatment with cabozantinib.
    • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
    • Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other checkpoint inhibitors previously.
    • Radiation therapy for bone metastasis ≤ 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
    • 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 4 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.
    • Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
    • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
    • Low-dose low molecular weight heparins (LMWH) are permitted.
    • Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
    • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 × ULN within 14 days before the first dose of study treatment.
    • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
    • Cardiovascular disorders:
    • Ongoing congestive heart failure exacerbation or New York Heart Association Class 4, unstable angina pectoris, serious cardiac arrhythmias.
    • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment. Uncontrolled hypertension needs to be determined based on persistently high blood pressure readings over more than 24 hours and should NOT be based on the blood pressure readings from one clinic visit. Blood pressure readings done at home or by primary care providers are acceptable. If a blood pressure reading on the day of screening is high, but there are documented acceptable ( ≤150 mm Hg systolic and ≤100 mm Hg diastolic) blood pressure readings prior to or after the screening visit (with or without the use of anti-hypertensive medications), patient will not be considered to have uncontrolled hypertension.
    • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
    • Class 3 congestive heart failure
    • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
    • The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
    • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
    • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
    • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
    • Lesions invading or encasing any major blood vessels.
    • Other clinically significant disorders that would preclude safe study participation.
    • Serious non-healing wound/ulcer/bone fracture.
    • Uncompensated/symptomatic hypothyroidism.
    • Moderate to severe hepatic impairment (Child-Pugh B or C).
    • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
    • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
    • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
    • Diagnosis of another malignancy within 2 years before first dose of study treatment, with the exception of those determined by the treating investigator to have a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated surgically with curative intent, localized prostate cancer treated with curative intent and/or no intent for further treatment, or incidental prostate cancer)
    • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
    • Has active autoimmune disease currently requiring systemic treatment with high dose corticosteroids (dose more than physiologic replacement doses equivalent to prednisone 10 mg daily) or (disease modifying immunosuppressive agents). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, intranasal, inhaled, topical steroids, or local steroid injection) is not considered an exclusion.
    • Active autoimmune disease that might deteriorate significantly when receiving an immuno-stimulatory agent per treating physician's clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
    • Prior organ transplantation including allogenic stem-cell transplantation.
    • Has known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
    • Has an active infection currently requiring systemic (intravenous) antibiotic therapy.
    • Has a known history of active TB (Bacillus Tuberculosis).
    • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
    • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    • Active and inactive vaccinations within 4 weeks of the first dose of pembrolizumab and while on trial is prohibited.
    • Known prior severe hypersensitivity to investigational products or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
    • 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.
    • Subjects taking prohibited medications as described in Section 6.8. A washout period of prohibited medications for a period of at least two weeks or as clinically indicated should occur prior to the start of treatment.
    • Inability to swallow tablets or evidence of impaired intestinal absorption Previous systemic chemotherapy treatment for urothelial carcinoma, with the exception of perioperative chemotherapy treatment alone or with concurrent radiation within 6 months prior to treatment.

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • Efficacy and Safety of Neoadjuvant Chemotherapy With Dose Dense MVAC Followed by Radical Surgery in Patients With MIBC and Locally Advanced Urothelial Carcinoma of Bladder: Phase II, Single-arm Study

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    Efficacy and Safety of Neoadjuvant Chemotherapy With Dose Dense MVAC Followed by Radical Surgery in Patients With MIBC and Locally Advanced Urothelial Carcinoma of Bladder: Phase II, Single-arm Study


    Condition: Muscle Invasive Bladder Cancer, Urothelial Carcinoma, Neoadjuvant Chemotherapy

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04047693

    Sponsor: Pusan National University Yangsan Hospital

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    1. Patients with histologically or cytologically confirmed urothelial cancer of bladder.
    2. Locally advanced status for planning surgical treatment (Bladder, confirm muscle invasiveness using TURBT, or cT3-4a and N1-3 using imaging studies)
    3. Age 18 years or older
    4. Eastern Cooperative Oncology Group performance status 0-1
    5. Adequate organ and bone marrow function for cisplatin based chemotherapy A. Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9 g/dL) B. Adequate renal function: creatinine < 1.5 x upper normal limit (UNL) or creatinine clearance(Ccr) using Cockroft and Gault formula ≥ 50 ml/min C. Adequate hepatic function: bilirubin < 1.5 x UNL, AST/ALT levels <5.0 x UNL, alkaline phosphatase < 5 x UNL (except in case of bone metastasis without any liver disease)
    6. Women should use contraceptive medication for 6 months after the end of the study or she would be post-menopause status. Men should consent with the contraception for 6 months after the end of the study or he would be infertile.
    7. Patients should sign a written informed consent before study entry.

    Exclusion Criteria:

    1. Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
    2. Excess of 4 weeks after initial imaging studies. But, allow the patients to enrollment of study if they is reassessed and reconfirm the localized status using subsequent imaging studies. In this case, clinical stage is decided as following imaging studies.
    3. Prior systemic chemotherapy (But prior intravesical chemotherapy was allowed)
    4. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
    5. History of treatment with drugs of another clinical trial within 30 days before enrollment.
    6. Concomitant severe medical, surgical, or psychiatric disease or problems which can affect the results of the clinical trial or have possibilities of unexpected medical problems caused be the drug of clinical trial A. Unstable angina, myocardial infarction, uncontrolled arrhythmias, symptomatic angina pectoris, cardiac failure within the previous 6 months B. Active infection which would compromise the patients C. Liver cirrohosis or chronic active hepatitis D. Poor pulmonary function (DLCO ≤ 50% of normal or resting O2 saturation ≤ 90%) E. Clinically significant hemoptysis or gastrointestinal bleeding within previous 6 months F. Major psychiatric disorders or other inadequate psychiatric problems according to the physicians decision
    7. History of another malignancy (but treated malignancy at least two years before enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid carcinoma are allowed even diagnosed less than 2 years before enrollment).
    8. Pregnant or lactating women, women of childbearing potential not employing adequate contraception

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • Familial and Atypical Urothelial Cancer Registry

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    A Genotype-Phenotype Urothelial Cancer Registry


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

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT00902590

    Sponsor: Memorial Sloan Kettering Cancer Center

    Phase:

    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.

    View trial on ClinicalTrials.gov


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    Published December 12, 2016
  • 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

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT01050504

    Sponsor: University of Washington

    Phase:

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02969083

    Sponsor: The European Uro-Oncology Group

    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 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
    • 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 4 years ago.
    • Concomitant muscle invasive bladder cancer
    • Patients who have been or still are on methotrexate treatment.

    View trial on ClinicalTrials.gov


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    Published November 30, 2018
  • 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
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02052778

    Sponsor: Taiho Oncology, Inc.

    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)

    View trial on ClinicalTrials.gov


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    Published July 28, 2019
  • Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) With Pembrolizumab, in Subjects Who Have Failed Cisplatin-Based Chemotherapy With Locally Advanced (Unresectable) or Metastatic Transitional Cell Cancer (TCC) of the Urothelium

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    Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) With Pembrolizumab, in Subjects Who Have Failed Cisplatin-Based Chemotherapy With Locally Advanced (Unresectable) or Metastatic Transitional Cell Cancer (TCC) of the Urothelium


    Condition: Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Unresectable Renal Pelvis Urothelial Carcinoma, Unresectable Ureter Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03935347

    Sponsor: Roswell Park Cancer Institute

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • The subject must understand the requirements of the study and voluntarily sign the informed consent form (ICF)
    • All subjects must have a histologically confirmed unresectable TCC (including renal pelvis, ureters, urinary bladder, and urethra)
    • Failed one and only one line of cisplatin-based chemotherapy per FDA guidelines.
    • Subjects must have an area of tumor amenable to excisional biopsy for the generation of TIL separate from, and in addition to , a target lesion to be used for response assessment.Have at least one resectable lesion to generate TILs
    • At least one measurable target lesion as defined by RECIST version 1.1
    • An Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
    • Estimated life expectancy of >= 6 months
    • Adequate bone marrow function
    • Adequate organ function
    • Subjects must be seronegative for the human immunodeficiency virus (HIV)
    • Recovered from all prior anticancer therapy-related AEs to grade 1 or less
    • Negative serum pregnancy test (female subjects of childbearing potential)
    • Subjects of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 12 months after the completion of the study treatment regimen
    • Must be able and willing to comply with the study visit schedule and protocol requirements including long-term follow-up

    Exclusion Criteria:

    • Have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or localized prostate cancer and non-melanoma skin cancer that has been adequately treated)
    • Have received prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen
    • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway-targeting agents
    • Chemotherapy or radiotherapy with projected completion within 4 weeks of initiating study treatment
    • Bisphosphonate therapy for symptomatic hypercalcemia
    • Have had 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
    • Active or prior documented autoimmune or inflammatory disorders
    • Subjects who have any form of human immondeficiency virus (HIV)infection
    • Have severe infections within 4 weeks before initiation of study treatment
    • Have received a live or attenuated vaccine within 28 days of the non-myeloablative lymphodepletion (NMA-LD regimen)
    • Subjects with a history of hypersensitivity reaction(s) to any component of the LN-145 therapy and/or the other study drugs
    • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 450 msec for males (and >= 470 msec for females) calculated from 3 electrocardiograms (ECGs) (within a 30-minute timeframe) or history of familiar long-QT syndrome
    • Subjects who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association functional classification class II or higher
    • Serious illnesses or medical conditions, which would pose increased risk for study participation and/or compliance with the protocol
    • Known clinically significant liver disease
    • Have obstructive or restrictive pulmonary disease and have a documented FEV1 (forced expiratory volume in 1 second) of =< 60%
    • Subjects with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
    • Subjects who are pregnant or breastfeeding
    • Active infection including tuberculosis (TB), hepatitis B, hepatitis C, or human immunodeficiency virus
    • Treatment with any other investigational agent within 4 weeks before initiation of study treatment

    View trial on ClinicalTrials.gov


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    Published May 2, 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02826564

    Sponsor: University Hospital, Ghent

    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.

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02780687

    Sponsor: Boehringer Ingelheim

    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

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03547973

    Sponsor: Immunomedics, Inc.

    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.
    • Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
    • 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
    • Cohort 3: Has active autoimmune disease requiring systemic treatment with steroids or other immunosuppressive agent or any condition that in the Investigator's judgment precludes treatment with pembrolizumab
    • Cohort 3: Has received a live vaccine within 30 days prior to the first dose of study drug(s)
    • Cohort 3: Has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis
    • Cohort 3: Has received anti-PD-1/PD-L1 therapy previously

    View trial on ClinicalTrials.gov


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    Published February 16, 2019
  • Phase II Study of Avelumab in Combination With AXL Inhibitor AVB-S6-500 in Patients With Advanced Urothelial Carcinoma

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    Phase I/II Study of Avelumab in Combination With AXL Inhibitor AVB-S6-500 in Patients With Advanced Urothelial Carcinoma


    Condition: Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04004442

    Sponsor: University of Oklahoma

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    1. Age ≥18 years
    2. Histologically confirmed locally advanced unresectable (T4b or N2/N3 disease) or metastatic urothelial cancer (including renal pelvis, ureters, urinary bladder, urethra).
    3. Eligible patients must have had either:
    4. Progressed after treatment with at least 1 prior platinum-containing regimen, (e.g., received at least 2 cycles of cisplatin or carboplatin-based regimen) for inoperable locally advanced unresectable or metastatic urothelial carcinoma, OR
    5. Unable to tolerate platinum (cisplatin or carboplatin) based chemotherapy due to toxicity, OR
    6. Experienced disease progression or recurrence within 12 months of completion of neoadjuvant or adjuvant cisplatin-based chemotherapy, OR
    7. Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology group (ECOG) performance status 2, grade ≥2 neuropathy, GFR<60 mL/Hr, grade ≥2 hearing loss and New York Heart Association class III or worse congestive heart failure.
    8. Available pretreatment baseline tumor specimen or willingness to undergo biopsy of primary or metastatic lesion if archived specimen is not available.
    9. ECOG performance status of ≤2
    10. At least one measurable lesion by RECIST version 1.1
    11. Patients who are able to understand and sign the informed consent form.
    12. Ability to comply with protocol
    13. Adequate hematologic and end-organ function per protocol
    14. For women of childbearing potential: Negative serum or urine pregnancy test at screening.
    15. For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drug

    Exclusion Criteria:

    1. Concurrent systemic treatment with an anticancer treatment or investigational drug within 28 days. Palliative radiation to symptomatic primary tumor or metastases is permitted as long as there are other measurable lesions present outside of the radiation field.
    2. Prior therapy with anti-PD-1 or PD-L1 agents.
    3. Concurrent systemic therapy with corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive agents within 28 days before starting trial drug. Short-term administration of systemic steroids (less than 7 days), adrenal replacement steroid doses (≤10 mg daily prednisone equivalent), topical, intranasal and inhaled steroid use is permitted.
    4. Patients with untreated or symptomatic central nervous metastases will be excluded. Appropriately treated CNS metastases with either surgery or radiation therapy are permitted to participate in the study.
    5. Active second malignancy or previous history of malignant disease (other than urothelial carcinoma) diagnosed within the last 3 years, with the exclusion of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ and prostate adenocarcinoma with Gleason score ≤7, pT2b.
    6. Prior organ transplantation, including allogenic stem-cell transplantation.
    7. Known history of testing positive for HIV/AIDS, HBV, or HCV (including acute and chronic infection).
    8. Known hypersensitivity to monoclonal antibody or any biologic drug, history of anaphylaxis, or uncontrolled asthma.
    9. Persisting toxicity related to prior therapy that was > grade 1; grade ≤2 sensory neuropathy is allowed.
    10. Pregnant or lactating, or intending to become pregnant during the study a. Women who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or surgically sterile must have a negative pregnancy test result within 14 days prior to the first dose of study treatment.
    11. Diagnosis of active autoimmune disease requiring systemic immunosuppression. Patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring systemic immunosuppression are eligible.
    12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
    13. Active infection requiring systemic therapy.
    14. Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
    15. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study.
    16. Other severe acute or chronic medical conditions per protocol

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • Phase II Study of Radiation Therapy and Anti-PD-L1 Checkpoint Inhibitor (Durvalumab) With or Without Anti-CTLA-4 Inhibition (Tremelimumab) in Patients With Unresectable, Locally Advanced, or Metastatic Urothelial Bladder Cancer That Are Ineligible or Refu

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    Phase II Study of Radiation Therapy and Anti-PD-L1 Checkpoint Inhibitor (Durvalumab) With or Without Anti-CTLA-4 Inhibition (Tremelimumab) in Patients With Unresectable, Locally Advanced, or Metastatic Urothelial Bladder Cancer That Are Ineligible or Refusing Chemotherapy


    Condition: Bladder Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03601455

    Sponsor: Jonsson Comprehensive Cancer Center

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
    • cT2
    • T4 or metastatic (N+ or M+) urothelial bladder cancer. Mixed histologies with predominant urothelial pattern are allowed. Patients with localized disease must either refuse cystectomy or be deemed not ideal cystectomy candidates.
    • If metastatic disease present patients must have an intact, symptomatic bladder tumor, appropriate for palliative RT to the bladder.
    • Measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. Thus, patients with metastatic disease must have at least 1 lesion, not previously irradiated, that can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes which must have a short axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurement as per RECIST v1.1 guidelines.
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1/
    • Life expectancy of >= 12 weeks.
    • Patients must be ineligible for or refuse cisplatin-based chemotherapy. Cisplatin ineligibility is defined as meeting 1 of the following criteria:
    • Creatinine clearance (calculated or measured) < 60 mL/min
    • Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 audiometric hearing loss
    • CTCAE grade 2 or higher peripheral neuropathy
    • New York Heart Association class III heart failure
    • Any other criteria deemed by the investigator to make the patient unsuitable for cisplatin-based chemotherapy
    • Note: The reason for cisplatin ineligibility must be documented. Patients may refuse cisplatin-based chemotherapy after an informed discussion of the risks and benefits, and the reason for refusal must be documented.
    • Subjects must consent to provide an archived tumor specimen from within 12 months prior to study entry (ie, from subject signing consent to participate in the study) for immunologic characterization. If not available, subjects should have at least 1 lesion amenable to biopsy and consent to provide a pre-treatment fresh biopsy. Tumor lesions used for biopsy should not be lesions used as target lesions. Additional archival tissue from beyond 12 months prior to study entry is also requested, if available, to support exploratory analyses.
    • Hemoglobin >= 9.0 g/dL
    • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (>= 1500 per mm^3)
    • Platelet count >= 100 x 10^9/L (>= 100,000 per mm^3)
    • Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert?s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
    • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x ULN
    • Serum creatinine clearance (CL) > 30 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
    • Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: >= 60 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
    • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
    • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visit and examinations and follow-up.

    Exclusion Criteria:

    • ECOG PS 2 or higher.
    • Prior cystectomy or definitive RT to the bladder.
    • 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, Wegner?s granulomatosis, Sjogren?s syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
    • Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave?s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
    • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are not excluded.
    • Patients with controlled type 1 diabetes mellitus on a stable dose of insulin regimen are not excluded.
    • Any chronic skin condition that does not require systemic therapy are not excluded.
    • Patients without active autoimmune disease in the last 5 years may be included after consultation with the study physician.
    • Patients with human immunodeficiency virus (HIV), active hepatitis B (HBV) or active hepatitis C (HCV)
    • Patients with past HBV infection or resolved HBV infection, defined as the presence of hepatitis B core antibody (HBc Ab) and absence of hepatitis B surface antigen (HBsAg) are eligible. HBV deoxyribonucleic acid (DNA) must be obtained in these patients prior to day 1 of therapy, but detection of HBV DNA in these patients will not exclude study participation.
    • Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
    • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
    • Previous investigational product (IP) assignment in the present study.
    • Current enrollment/participation in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
    • Prior radiation therapy to the abdomen or pelvis, including radiation therapy to the bladder, prostate, or rectum.
    • Any concurrent systemic chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (i.e. hormonal replacement therapy) is acceptable. Prior systemic therapies are allowed with a washout period of >= 45 days.
    • Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note biopsy and transurethral resection of the bladder tumor (TURBT) of the primary tumor is acceptable.
    • History of another primary malignancy except for:
    • Malignancy treated with curative intent and with no known active disease >= 3 years before the first dose of study drug and of low potential risk for recurrence.
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
    • Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ >> (Optional criteria that are dependent on the patient population under investigation.)
    • Note: Patients with incidental finding of early stage prostate cancer will not be eligible.
    • QT interval corrected for heart rate using Fridericia?s formula (QTcF) >= 470 ms calculated. Any clinically significant abnormalities detected require triplicate electrocardiography (ECG) results and a mean QT interval corrected for heart rate using Fridericia?s formula (QTcF) >= 470 ms calculated from 3 ECGs).
    • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
    • History of primary immunodeficiency.
    • History of allogeneic organ transplant.
    • History of hypersensitivity to durvalumab, tremelimumab, or any excipient.
    • History of hypersensitivity to the combination therapy of durvalumab and tremelimumab.
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
    • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis [TB] testing in line with local practice).
    • History of leptomeningeal carcinomatosis.
    • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab.
    • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
    • Brain metastases or spinal cord compression unless the patient?s condition is stable (asymptomatic, no evidence of new or emerging brain metastases) and off steroids for at least 14 days prior to the start of study treatment. Following radiotherapy and/or surgery, patients with suspected brain metastases at screening should have a magnetic resonance imaging (MRI)(preferred)/CT, preferably with IV contrast.
    • Subjects with uncontrolled seizures.
    • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.

    View trial on ClinicalTrials.gov


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    Published May 12, 2020
  • 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 Ureter Carcinoma, Metastatic Urethral Carcinoma, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Ureter Cancer AJCC v7, Stage III Urethral Cancer AJCC v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, Stage IV Ureter Cancer AJCC v7, Stage IV Urethral Cancer AJCC v7, Ureter Urothelial Carcinoma, Urethral Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02178241

    Sponsor: National Cancer Institute (NCI)

    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

    View trial on ClinicalTrials.gov


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    Published January 25, 2017

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