Bladder Cancer

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A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma


Condition: Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Renal Pelvis Carcinoma, Ureter Carcinoma, Urinary Bladder Carcinoma, Urethra Carcinoma, Muscle Invasive Bladder Cancer

Intervention:

  • Drug: Rucaparib

Purpose: The purpose of the ATLAS study is to determine how patients with locally advanced or metastatic urothelial carcinoma respond to treatment with rucaparib.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03397394

Sponsor: Clovis Oncology, Inc.

Primary Outcome Measures:

  • Measure: Objective response rate (ORR)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of response (DOR)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Progression-free survival (PFS)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Number of participants with treatment-related Adverse Events (AEs) as assessed by CTCAE v4.03 as a measure of safety and tolerability
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Number of participants with serious AEs as a measure of safety and tolerability
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Number of participants with worsening laboratory values as a measure of safety and tolerability
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Trough plasma PK (Cmin) of rucaparib based on sparse sampling
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:

Estimated Enrollment: 200

Study Start Date: June 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Have histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
  • Received 1 or 2 prior standard of care regimens for advanced or metastatic disease
  • Confirmed radiologic disease progression during or following recent treatment
  • Mandatory biopsy is required during screening
  • Measurable disease per RECIST v1.1
  • Adequate organ function
  • ECOG 0 or 1

Exclusion Criteria:

  • Prior treatment with a PARP inhibitor
  • Symptomatic and/or untreated CNS metastases
  • Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib

Contact:

  • Clovis Oncology Clinical Trial Navigation
  • 1-855-262-3040 (USA)

Locations:

  • University of California, Los Angeles (UCLA)
  • Los Angeles California 90095 United States
  • Saint John's Health Center - John Wayne Cancer Institute (JWCI)
  • Santa Monica California 90404 United States
  • Eastern Connecticut Hematology & Oncology Associates (ECHO)
  • Norwich Connecticut 06360 United States
  • Indiana University - Melvin and Bren Simon Cancer Center (IUSCC)
  • Indianapolis Indiana 46202 United States
  • The University of Iowa and Holden Comprehensive Cancer Center
  • Iowa City Iowa 52242 United States
  • Ochsner Cancer Institute
  • New Orleans Louisiana 70121 United States
  • University of Maryland, Marlene and Stewart Greenebaum Cancer Center
  • Baltimore Maryland 21201 United States
  • University of Michigan
  • Ann Arbor Michigan 48109 United States
  • Comprehensive Cancer Centers of Nevada (CCCN)
  • Las Vegas Nevada 89169 United States
  • University of New Mexico UNM Cancer Research and Treatment Center
  • Albuquerque New Mexico 87102 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • Providence Portland Medical Center
  • Portland Oregon 97213 United States
  • Atlantic Urology Clinics
  • Myrtle Beach South Carolina 29572 United States
  • University Oncology & Hematology
  • Chattanooga Tennessee 37403 United States
  • Urology Associates
  • Nashville Tennessee 37209 United States
  • University of Texas, UT Health Science Center
  • Houston Texas 77030 United States
  • University of Utah, Huntsman Cancer Institute
  • Salt Lake City Utah 84112 United States
  • University of Virginia, Emily Couric Clinical Center
  • Charlottesville Virginia 22908 United States
  • University of Washington / Seattle Cancer Care Alliance
  • Seattle Washington 98109 United States
  • Universidad de Navarra - Clinica Universitaria de Navarra
  • Pamplona Navarre 31008 Spain
  • Hospital del Mar
  • Barcelona 08003 Spain
  • Hospital Universitari Vall d'Hebron de Barcelona
  • Barcelona 08035 Spain

View trial on ClinicalTrials.gov


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Phase 2 Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations


Condition: Metastatic Urothelial Cancer

Intervention:

  • Drug: Olaparib

Purpose: This is a single arm open label multi-institutional phase II trial of olaparib monotherapy in subjects with metastatic urothelial cancer harboring somatic DNA damage response (DDR) alterations. The primary objective of the study is to estimate the objective response rate (per RECIST 1.1) to treatment with olaparib.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03448718

Sponsor: Matthew Galsky

Primary Outcome Measures:

  • Measure: Objective Response Rate
  • Time Frame: 36 Months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-Free Survival
  • Time Frame: 36 Months
  • Safety Issue:

Estimated Enrollment: 30

Study Start Date: April 17, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of ≤ 1 within 14 days prior to registration. Cisplatin-ineligible chemotherapy-naïve subjects (see inclusion criteria #8) may have an ECOG Performance Status of ≤ 2.
  • Histological or cytological evidence/confirmation of urothelial cancer.
  • Metastatic and/or unresectable (cT4b) urothelial cancer.
  • Metastatic disease evaluable on imaging studies. Subjects may have measurable disease according to RECIST 1.1 or bone-only disease within 30 days prior to registration.
  • NOTE: Bone-only subjects are eligible if their disease can be documented/ evaluated by bone scans, CT or MRI. Their disease will be assessed using MD Anderson criteria.34
  • NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation.
  • Somatic alteration in one of the following DDR genes as determined by genomic sequencing performed in a Clinical Laboratory Improvement Amendments (CLIA) laboratory. Somatic alterations will include nonsense, frameshift, splice-site or missense mutations or homozygous deletions. Subjects with alterations in DDR genes not included in the list below will be considered on a case by case basis after discussion with the sponsor-investigator. Subjects with germline alterations in DDR genes will be considered on a case by case basis and will be reviewed by the sponsor-investigator. At least 6 subjects will have BRCA or ATM alterations.
  • Nucleotide Excision Repair: ERCC2, ERCC3,ERCC4, ERCC5, ERCC6
  • Homologous Recombination: BRCA1, RAD52, BRCA2, RAD54L, RAD50, NBN RAD51, MRE11A, RAD51B, RAD51D, RAD51C, CTIP
  • DNA Sensor: ATM, ATR, MDC1, ATRX, CHEK1, CHEK2
  • Fanconi Anemia Pathway: PALB2, FANCE, BRIP1, FANCF, FANCA, FANCG FANCB, BLM, FANCC, FANCD2
  • Base Excision Repair: XRCC2, XRCC3, XRCC4, XRCC5, XRCC6
  • Other: MUTYH, RECQL4, POLQ, POLE, WRN
  • A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic
  • Subjects must have progressed despite at least 1 prior line of treatment for metastatic and/or unresectable urothelial cancer. However, cisplatin-ineligible (defined by a calculated creatinine clearance of >30 but < 60 mL/min OR CTCAE v4 Grade ≥ 2 audiometric hearing loss OR CTCAE v4 Grade ≥ 2 peripheral neuropathy OR ECOG PS = 2), and chemotherapy-naïve subjects are also eligible.
  • Prior cancer treatment (systemic therapy or radiation therapy) must be completed at least 3 weeks prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
  • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  • Hemoglobin (Hgb) ≥ 10 g/dL
  • Platelets ≥ 100 x 109/L
  • Calculated creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases)
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases)
  • Female subjects must be postmenopausal or there must be evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
  • Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 30 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Males must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 90 days after treatment discontinuation.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
  • All subjects must have adequate archival tissue available prior to registration (i.e., at least 15 unstained slides or paraffin block). Archival tissue should represent invasive or metastatic urothelial cancer with a preference for metastatic tissue if available. Subjects without adequate tissue may be considered on a case by case basis after discussion with the sponsor-investigator.

Exclusion Criteria:

  • Active infection requiring systemic therapy.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Known additional malignancy that is active and/or progressive requiring treatment; subjects with other malignancies that have been definitively treated and who have been rendered disease free will be eligible.
  • Prior treatment with a PARP inhibitor, including olaparib.
  • Treatment with any investigational drug within 30 days prior to registration.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
  • Major surgery within 2 weeks of starting study treatment and subjects must have recovered from any effects of any major surgery.
  • Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan, history of pneumonitis, or any psychiatric disorder that prohibits obtaining informed consent.
  • Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Subjects with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  • Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

Contact:

  • Matthew Galsky, MD
  • 212-824-5452

Locations:

  • University of Chicago Medical Center
  • Chicago Illinois 60637 United States
  • Icahn School of Medicine at Mount Sinai
  • New York New York 10029-6542 United States

View trial on ClinicalTrials.gov


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A Phase 1 Dose-Escalation Study of Intravesical MK-3475 and Bacillus Calmette-Guerin (BCG) in Subjects With High Risk and BCG-Refractory Non-Muscle-Invasive Bladder Cancer


Condition: Recurrent Bladder Carcinoma, Stage 0a Bladder Urothelial Carcinoma, Stage 0is Bladder Urothelial Carcinoma, Stage I Bladder Cancer

Intervention:

  • Biological: BCG Solution
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab
  • Other: Pharmacological Study

Purpose: The purpose of this study is to evaluate the efficacy (the effect of drug on tumor) and the tolerability (the effect of drug on the body) of pembrolizumab, when given as a single agent in patients with bladder tumors. Another purpose of the study is to see what tumor characteristics are associated with increased efficacy of the pembrolizumab. Pembrolizumab (MK-3475) is an antibody (a human protein that sticks to a part of the tumor and/or immune cells) designed to allow the body's immune system to work against tumor cells. Pembrolizumab is Food and drug Administration (FDA) approved for the treatment of advanced melanoma (a type of skin cancer) and some types of lung cancer. It is not yet approved by the United States Food and Drug Administration (USFDA) for bladder cancer, hence it is considered an investigational agent for this disease.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02808143

Sponsor: Northwestern University

Primary Outcome Measures:

  • Measure: Maximum Tolerated Dose (MTD)
  • Time Frame: Up to 9 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Dose Limiting Toxicities (DLTs)
  • Time Frame: Up to 9 weeks
  • Safety Issue:
  • Measure: Incidence of adverse events
  • Time Frame: Up to 30 days from the last dose of study drug
  • Safety Issue:

Estimated Enrollment: 27

Study Start Date: February 10, 2017

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Patients must have a histologically documented recurrence of non-muscle-invasive bladder carcinoma (T1HG, T1HG after repeat transurethral resection [reTUR]) or BCG refractory; if patient has received BCG they can be Ta, Tis, or T1)
  • Patients must have persistent high grade disease OR be BCG refractory, defined as either:
  • Recurrence within 6 months of receiving at least 2 courses of intravesical BCG (at least 5 or 6 inductions and at least 2 or 3 maintenance doses) or
  • T1 high grade disease at the first evaluation following induction BCG alone (at least 5 of 6 induction doses)
  • Patients must agree to provide tissue from archival biopsy samples or newly obtained excisional biopsy of a tumor lesion
  • NOTE: Patients who do not have available specimens from previous biopsy or do not agree to provide this tissue are not eligible; cytological specimens will not be acceptable; availability of tissue must be confirmed at the time of registration, but the actual sample does not have to be received in order to complete registration
  • Patients must have received one course of induction treatment with BCG (4-6 weekly doses), irrespective of the interval since last treatment; patients are allowed to have received any number of prior chemotherapy instillations
  • NOTE: Patients may have received prior intravesical interferon
  • All patients must have imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI]) documenting normal upper urinary tracts and absence of locally advanced bladder cancer within 60 days prior to study registration
  • Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Absolute neutrophil count (ANC) >= 1,500 /mcL within 14 days prior to registration
  • Platelets >= 100,000 / mcL within 14 days prior to registration
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L within 14 days prior to registration
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated (creatinine clearance should be calculated per institutional standard) creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN within 14 days prior to registration
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN within 14 days prior to registration
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN within 14 days prior to registration
  • 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 within 14 days prior to registration
  • Activated PTT (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 within 14 days prior to registration
  • Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;
  • NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria
  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • FOCBP must have a negative urine or serum pregnancy test within 7 days 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
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria:

  • Patients who have had chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day -14 or who have not recovered (to =< grade 1 or baseline) from adverse events due to a previously administered agent are not eligible
  • Note: subjects with =< grade 2 neuropathy are an exception to this criterion and do qualify for the study
  • Note: if subject received major surgery within 4 weeks prior to day -14, they must have recovered adequately from the toxicity and/or complications per PI discretion
  • Patients may not be receiving any other investigational agents within 4 weeks of the first dose of treatment
  • Patients who have received a prior monoclonal antibody within 4 weeks prior to study day -14 or who have not recovered (to =< grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier are not eligible
  • Patients who have a diagnosis of immunodeficiency (per PI discretion) or who have received treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to study registration are not eligible
  • NOTE: patients who have received acute, low-dose, systemic immunosuppressant medications (eg, one-time dose of dexamethasone for nausea) may be enrolled in the study; the use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) is allowed
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 are not eligible AND/OR patients who have had prior exposure to compounds of similar chemical or biologic composition to MK-3475 are not eligible
  • Patients who have documentation of an uncontrolled intercurrent illness (as noted in their medical records) including, but not limited to any of the following, are not eligible
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure (New York Heart Association cardiac disease class III or IV)
  • Unstable angina pectoris
  • Myocardial infarction within the previous 3 months
  • Unstable cardiac arrhythmias
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Female patients who are pregnant or nursing are not eligible
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to BCG are not eligible
  • Patients who have had an active infection requiring systemic therapy within 1 week prior to day -14 are not eligible UNLESS they are symptom-free and have a negative culture at the time of dosing on day -14
  • Patients who received a live, attenuated vaccine within 4 weeks before study registration or are anticipated to require such a live attenuated vaccine are not eligible; NOTE: Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to study registration or at any time during the study
  • Patients who are known to be (i.e. documented in medical records) human immunodeficiency virus (HIV) positive are not eligible
  • Patients with active tuberculosis are not eligible
  • Patients with known active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C are not eligible
  • NOTE: patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible; HBV deoxyribonucleic acid (DNA) must be obtained in these patients 14 days prior to study registration
  • NOTE: patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins are not eligible
  • Patients with an active autoimmune disease requiring systemic treatment within 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
  • Patients with a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
  • Patients with history of interstitial lung disease or active, non-infectious pneumonitis are not eligible
  • NOTE: history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to study registration are not eligible
  • Patients who received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) are not eligible
  • Patients who have a history of prior malignancy are not eligible; please NOTE the following exceptions when patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
  • Basal cell carcinoma of the skin
  • Squamous cell carcinoma of the skin
  • In situ cervical cancer
  • Patients who have a history of an allogeneic tissue/solid organ transplant are not eligible

Contact:

  • Study Coordinator
  • (312)695-1301

Location:

  • Northwestern University
  • Chicago Illinois 60611 United States

View trial on ClinicalTrials.gov


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A Phase 2, Randomized, Open-label Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined With Intravesical BCG in Participants With BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer


Condition: Bladder Cancer, Bladder Tumors, Neoplasms, Bladder

Intervention:

  • Biological: Nivolumab
  • Biological: BCG
  • Drug: BMS-986205

Purpose: A study to evaluate Nivolumab or Nivolumab Plus Experimental Medication BMS-986205 with or without BCG in BCG-Unresponsive non-muscle invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03519256

Sponsor: Bristol-Myers Squibb

Primary Outcome Measures:

  • Measure: Proportion of carcinoma in situ (CIS) participants with complete response (CR), per Pathology Review Committee (PRC)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Duration of complete response (DOCR), per PRC, in CIS participants with CR
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Event Free Survival (EFS), per PRC, for all non-CIS participants
  • Time Frame: Up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free Survival (PFS)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Incidence of Adverse Events (AEs)
  • Time Frame: Up to 15 months
  • Safety Issue:
  • Measure: Incidence of Serious Adverse Events (SAEs)
  • Time Frame: Up to 15 months
  • Safety Issue:
  • Measure: Incidence of AEs leading to discontinuation
  • Time Frame: Up to 15 months
  • Safety Issue:
  • Measure: Incidence of deaths
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Incidence of laboratory abnormalities
  • Time Frame: Up to 15 months
  • Safety Issue:

Estimated Enrollment: 436

Study Start Date: May 25, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Pathologically demonstrated BCG-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) defined as CIS with or without papillary component, any T1, or Ta high-grade lesions
  • Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria:
  • Sign of locally advanced disease or metastatic bladder cancer
  • Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
  • Prior immuno-oncology therapy Other protocol defined inclusion/

Exclusion Criteria:

  • Sign of locally advanced disease or metastatic bladder cancer
  • Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
  • Prior immuno-oncology therapy Other protocol defined inclusion/exclusion criteria could apply

Contact:

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

Locations:

  • Local Institution
  • Phoenix Arizona 85054 United States
  • Local Institution
  • Los Angeles California 90033 United States
  • Local Institution
  • Riverside California 92505 United States
  • Local Institution
  • San Francisco California 94158 United States
  • Local Institution
  • Atlanta Georgia 30322 United States
  • The University Of Chicago
  • Chicago Illinois 60637 United States
  • Local Institution
  • Wichita Kansas 67226 United States
  • Local Institution
  • Shreveport Louisiana 71106 United States
  • Local Institution
  • Baltimore Maryland 21287 United States
  • Local Institution
  • Ann Arbor Michigan 48109 United States
  • Local Institution
  • Minneapolis Minnesota 55455 United States
  • Local Institution
  • Omaha Nebraska 68114 United States
  • Local Institution
  • Voorhees New Jersey 08043 United States
  • Local Institution
  • New York New York 10016 United States
  • Local Institution
  • New York New York 10032 United States
  • Local Institution
  • New York New York 10065 United States
  • Local Institution
  • Columbus Ohio 43210 United States
  • Local Institution
  • Springfield Oregon 97477 United States
  • Local Institution
  • Bala-Cynwyd Pennsylvania 19004 United States
  • Local Institution
  • Hershey Pennsylvania 17033 United States
  • Local Institution
  • Charleston South Carolina 29425 United States
  • Local Institution
  • Myrtle Beach South Carolina 29572 United States
  • Local Institution
  • Chattanooga Tennessee 37403 United States
  • Local Institution
  • Nashville Tennessee 37232 United States
  • Local Institution
  • Dallas Texas 75231 United States
  • Local Institution
  • Houston Texas 77030 United States
  • Local Institution
  • Lubbock Texas 79430-0002 United States
  • Local Institution
  • San Antonio Texas 78229 United States
  • Local Institution
  • Virginia Beach Virginia 23462 United States
  • Local Institution
  • Capital Federal Buenos Aires 1426 Argentina
  • Local Institution
  • Capital Federal Buenos Aires C1122AAN Argentina
  • Local Institution
  • Ciudad Autonoma de Buenos Aires Buenos Aires 1280 Argentina
  • Local Institution
  • Viedma RIO Negro 8500 Argentina
  • Local Institution
  • Cordoba 5000 Argentina
  • Local Institution
  • Fortaleza Ceara 60130-241 Brazil
  • Local Institution
  • Porto Alegre RIO Grande DO SUL 91350-200 Brazil
  • Local Institution
  • Campinas SAN Paulo 13075-460 Brazil
  • Local Institution
  • Itacorubi, Florianopolis Santa Catarina 88034 Brazil
  • Local Institution
  • Jau SAO Paulo 17210-080 Brazil
  • Local Institution
  • Sao Paulo 01246-000 Brazil
  • Local Institution
  • St. John's Newfoundland and Labrador A1B 3V6 Canada
  • Local Institution
  • Toronto Ontario M4N 3M5 Canada
  • Local Institution
  • Toronto Ontario M5G 1Z5 Canada
  • Local Institution
  • Sherbrooke Quebec J1H 5N4 Canada
  • Local Institution
  • Quebec G1R 2J6 Canada
  • Local Institution
  • Santiago Metropolitana Chile
  • Local Institution
  • Angers 49100 France
  • Local Institution
  • Suresnes 92151 France
  • Local Institution
  • Milano 20133 Italy
  • Local Institution
  • Modena 41100 Italy
  • Local Institution
  • Napoli 80131 Italy
  • Local Institution
  • Pisa 56126 Italy
  • Local Institution
  • Tuxtla Gutierrez Chiapas 290838 Mexico
  • Local Institution
  • Ciudad de Mexico Distrito Federal 06100 Mexico
  • Local Institution
  • Df Distrito Federal 06720 Mexico
  • Local Institution
  • Amsterdam 1066CX Netherlands
  • Local Institution
  • Nijmegen 6525 GA Netherlands
  • Local Institution
  • Utrecht 3584CX Netherlands
  • Local Institution
  • Omsk 644013 Russian Federation
  • Local Institution
  • Saint-Petersburg 194044 Russian Federation
  • Local Institution
  • Barcelona 08025 Spain
  • Local Institution
  • Madrid 28041 Spain
  • Local Institution
  • Malaga 29010 Spain
  • Local Institution
  • Istanbul 34000 Turkey
  • Local Institution
  • Istanbul 34214 Turkey
  • Local Institution
  • Istanbul 34300 Turkey
  • Local Institution
  • Chelmsford Essex CM1 7ET United Kingdom
  • Local Institution
  • Lancaster LA1 4RP United Kingdom
  • Local Institution
  • London N18 1QX United Kingdom
  • Local Institution
  • London NW1 2BU United Kingdom
  • Local Institution
  • Southampton SO16 6YD United Kingdom

View trial on ClinicalTrials.gov


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A Phase I Single-Arm Study of the Combination of Durvalumab (MEDI4736) and Vicinium (Oportuzumab Monatox, VB4-845) in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With BCG


Condition: Urinary Bladder Neoplasms

Intervention:

  • Drug: Durvalumab
  • Drug: Vicinium

Purpose: Background: Non-muscle-invasive bladder cancer is in the early stages. But it usually comes back after treatment. The drugs Vicinium and Durvalumab may help the immune system find and destroy cancer cells. Objective: To test if the drugs Durvalumab and Vicinium together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder. Eligibility: People ages 18 and older who have bladder cancer that has not spread to the muscle in the bladder and was treated unsuccessfully with Bacillus Calmette-Guerin Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Tumor sample from previous surgery. If one is not available, they will have a biopsy: A small piece of tumor is removed. Cystoscopy to examine the inside of the bladder. This may include a biopsy or removing tumors. CT or MRI: They lie in a machine that takes pictures of the body. Electrocardiogram to test heart function Participants will receive Durvalumab and Vicinium in 2 phases: First phase: Durvalumab every 4 weeks and Vicinium once a week for 3 months Second phase: Durvalumab every 4 weeks and Vicinium once every other week Participants will have tumor samples taken every 3 months. They will have blood and urine tests throughout the study. Participants will continue treatment for up to 2 years. Participants will have a visit about 30 days after their last treatment. This includes blood and urine tests. It may include a cytoscopy or additional biopsies.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03258593

Sponsor: National Cancer Institute (NCI)

Primary Outcome Measures:

  • Measure: safety and tolerability
  • Time Frame: one year
  • Safety Issue:

Estimated Enrollment: 40

Study Start Date: June 7, 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum 100 Years
  • Gender: All

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed by NCI Laboratory of Pathology as high grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:
  • Carcinoma-in-situ (CIS) with or without papillary tumors
  • High-grade Ta or T1 disease based on a biopsy/TURBT performed within 12 weeks of the initial dose of study treatment. If multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks.
  • Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy.
  • Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the FDA: Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course). Please note exception above for persistent T1 disease. There is no upper limit on the amount of prior BCG a subject may have received.
  • Patients who have met eligibility criterion above must have received last BCG dose within a year of enrollment.
  • The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry.
  • Age >= 18 years at time of signing the informed consent form (ICF). Because no dosing or adverse event data are currently available on the use of Vicinium in combination with durvalumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. Furthermore, NMIBC does not occur in children.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
  • Platelet count >= 75 x 10^9/L (>75,000 per mm^3)
  • Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN).
  • AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional ULN
  • Creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  • Males: Creatinine CL (mL/min) =(Weight (kg) x (140 Age))/72 x serum creatinine (mg/dL)
  • Females: Creatinine CL (mL/min)= (Weight (kg) x (140 Age) x 0.85 )/72 x serum creatinine (mg/dL)
  • Female subjects must either be of non-reproductive potential (i.e., post-menopausal as described below) OR history of surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  • 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
  • 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, or had chemotherapy-induced menopause with last menses >1 year ago
  • The effects of Vicinium and durvalumab on the developing human fetus are unknown. For this reason, all sexually active subjects agree to use barrier contraception (i.e., condoms) while receiving study treatment and for 120 days following their last dose of study treatment. Female subjects of child-bearing potential and male subjects whose sexual partners are WOCBP agree to use barrier contraception and a second form of contraception while receiving study treatment and for 4 months following their last dose of study treatment. 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.
  • Written informed consent obtained from the subject prior to performing any protocol- related procedures
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Body weight > 30 kg

Exclusion Criteria:

  • Patients who are receiving any other investigational agents.
  • QT interval corrected for heart rate using Fridericia s formula (QTcF) >=470 ms. (Any clinically significant abnormalities detected require triplicate ECG results and a mean QT interval corrected for heart rate using Fridericia s formula (QTcF) >=470 ms calculated from 3 ECGs.)
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Vicinium or durvalumab or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, 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. Urinary tract infections (UTIs) are excluded from being an exclusion criterion for treatment unless they are grade 3 or higher.
  • Pregnant women are excluded from this study because it is unknown whether Vicinium and/or durvalumab have any teratogenic effects. In nursing mothers, breastfeeding should be discontinued as these medications may have the potential risk for adverse events in nursing infants secondary to treatment of the mother.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  • Evidence of non-bladder urothelial (transitional cell) carcinoma by biopsy, cytology, or radiological imaging within the past 2 years of treatment (e.g. upper tract transitional cell carcinoma, urethral urothelial carcinoma).
  • Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta, or T1 by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor causing the hydronephrosis.
  • Any other anticancer therapy (e.g., chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, radiation therapy, intravesical therapy, investigational agent) within 28 days of the first dose of study therapy (and within 6 weeks for nitrosourea or mitomycin C) other than a single dose of intravesical chemotherapy which is permitted between 28 days and 14 days prior to the first dose of study treatment.
  • The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer, localized prostate cancer on active surveillance, or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, 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.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn s disease], diverticulitis [with the exception of diverticulosis], 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 vitiligo or alopecia
  • Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormonal replacement
  • Any chronic skin condition that does not require systemic therapy
  • Subjects without active disease in the last 5 years may be included but only after consultation with the Principal Investigator
  • Subjects with celiac disease controlled by diet alone
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • History of hypersensitivity to durvalumab or any excipient
  • History of hypersensitivity to Vicinium or its components
  • Active infection with tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and PPD testing if indicated), hepatitis B (known positive HBV surface antigen (HBsAg) result, hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to the first dose of Vicinium or durvalumab
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Subjects with uncontrolled seizures
  • Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Subjects with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator.
  • Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal Investigator.

Contact:

  • Sonia E Bellfield, R.N.
  • (240) 760-6118

Location:

  • National Institutes of Health Clinical Center
  • Bethesda Maryland 20892 United States

View trial on ClinicalTrials.gov


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PhAse 1/2 StuDy of Modern ImmunotherApy in BCG-RelaPsing UroThelial Carcinoma of the BLADDER - (ADAPT-BLADDER) HCRN GU16-243


Condition: Urothelial Carcinoma, Bladder Cancer

Intervention:

  • Drug: Durvalumab
  • Radiation: External Beam Radiotherapy (EBRT)
  • Biological: Bacillus Calmette-Guérin (BCG)

Purpose: A multi-arm multi-stage (MAMS) phase 1/2 study. Phase 1 will be conducted in BCG-unresponsive NMIBC patients to establish the safety of durvalumab monotherapy (cohort 1) and durvalumab in combination with BCG (cohort 2a) and external beam radiation therapy (EBRT) (cohort 2b). Provided safety is demonstrated and recommended phase 2 doses (RP2D) are established in phase 1, the study will proceed to phase 2 testing. Phase 2 will be conducted in the BCG-relapsing NMIBC population. In phase 2, BCG-relapsing NMIBC subjects will be randomized between treatment arms examining intravesical BCG in combination with novel immunotherapy agents (durvalumab), novel immunotherapy in combination with radiation (durvalumab + EBRT), or retreatment with intravesical BCG. In addition to providing additional safety data on the combination regimens studied, phase 2 will provide preliminary efficacy profiles for BCG-relapsing NMIBC subjects with and without CIS treated with each regimen. For regimens demonstrating a tolerable safety profile and encouraging clinical activity in this phase 1/2 design, a randomized phase 3 trial of experimental arm therapy versus re-treatment with intravesical BCG therapy would be considered.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03317158

Sponsor: Noah Hahn, M.D.

Primary Outcome Measures:

  • Measure: Phase 1: Determine the recommended phase 2 dose (RP2D) of immunotherapy doublet combinations
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 6-month relapse-free survival (RFS) rates of BCG-relapsing non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy doublet combinations or BCG re-treatment
  • Time Frame: 6 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Phase 1: Characterize the 6-month relapse-free survival (RFS) rate of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy monotherapy or doublet combinations
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Assess the safety profile of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy monotherapy or doublet combinations by reporting the highest grade adverse event per patient, as assessed by CTCAE v4.0.
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 24-month relapse-free survival (RFS) rates of BCG-relapsing non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy doublet combinations or BCG re-treatment
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Phase 2: Identify significant associations between 6- and 24-month RFS rates and baseline tumor immunohistochemistry staining patterns of PD-L1 and other relevant mechanism of action targets for each drug studied within each study arm.
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 6-month relapse-free survival (RFS) rate of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with durvalumab
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 24-month relapse-free survival (RFS) rate of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with durvalumab.
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Assess the safety profile of BCG-relapsing non-muscle invasive bladder cancer subjects treated with immunotherapy monotherapy, doublet combinations or BCG re-treatment by reporting the highest grade adverse event per patient as assessed by CTCAE v4.0.
  • Time Frame: up to 24 months
  • Safety Issue:

Estimated Enrollment: 186

Study Start Date: November 21, 2017

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • (All Patients): Subject must meet all of the following applicable criteria to participate in this study:
  • Histologically confirmed non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 42 days of registration.
  • ECOG (WHO) performance status 0 or 1
  • Age ≥ 18 years old at time of consent
  • Adequate hematologic, hepatic, and renal function as defined by the following laboratory parameters:
  • White blood cell count (WBC) > 3.0 K/mm^3
  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm^3
  • Platelets ≥ 100 K/mm^3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum total bilirubin: ≤ 1.5 x ULN
  • ALT and AST ≤ 2.5 x ULN
  • Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
  • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if subject is female multiply the above by 0.85)
  • Subjects who give a written informed consent obtained according to local guidelines. Inclusion Criteria (Phase 1 Only):
  • In addition to the inclusion criteria required of all patients listed above, the following inclusion criteria are also required of patients enrolling to Phase 1 of the study.
  • BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy)
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations
  • Relapsed NMIBC within 6 months of last exposure to BCG
  • Prostatic urethra involvement of NMIBC Inclusion Criteria (Phase 2 Only):
  • In addition to the inclusion criteria required of all patients listed above, the following inclusion criteria are also required of patients enrolling to Phase 2 of the study. Intermediate or high-risk NMIBC defined according to modified EORTC risk criteria summarized as follows:
  • Low-risk Tumors Initial or recurrent tumor > 12 months after resection with all of the following:
  • Solitary tumor
  • Low-grade
  • < 3 cm
  • No CIS
  • Intermediate-Risk Tumors: All tumors not defined in the two adjacent categories (between the category of low- and high-risk).
  • High-risk Tumors: Any of the following:
  • T1 tumor
  • High-grade
  • CIS
  • Multiple and recurrent and large (> 3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors).
  • Documented recurrence within 15 months of last exposure to intravesical therapy.
  • Recurrence after 1 prior induction course of intravesical BCG. Inclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the inclusion criteria described of all patients listed above, the following inclusion criteria are also required of patients originally enrolled in Phase 2 of the study who are noted to have NMIBC in follow up and opt to cross-over to durvalumab monotherapy.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG
  • Prostatic urethra involvement of NMIBC Primary Exclusion Criteria: Exclusion Criteria (All Patients):
  • Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
  • Abdomen/Pelvis
  • CT scan
  • Chest
  • chest x-ray or CT scan
  • Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects 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.
  • Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
  • Subjects who have received prior therapy with PD-1 or PD-L1 directed agents.
  • Subjects who have had any prior radiation to the prostate or pelvis.
  • Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Clinically significant cardiac diseases, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias.
  • Clinically significant resting bradycardia.
  • Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
  • Cirrhosis
  • Active Infection (includes chronic active and chronic persistent).
  • Tuberculosis
  • Hepatitis B (known positive HBV surface antigen (HbsAg). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], 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:
  • Patients with vitiligo or alopecia.
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • Patients with celiac disease controlled by diet alone.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
  • Pregnant or breast-feeding women. Women of child-bearing potential must have a negative urine or serum test ≤ 14 days prior to starting study drug.
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception or abstinence. Highly effective contraception or abstinence must be used from the time of informed consent, throughout the trial and up to 180 days after the last dose of durvalumab (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). 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).
  • Fertile males not willing to use contraception or abstinence, as stated above. Contraception or abstinence must be followed from screening through 180 days after receipt of the final dose of durvalumab therapy.
  • Subjects unwilling or unable to comply with the protocol.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Exclusion Criteria (Phase 1 Only):
  • In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients in the section listed above. Exclusion Criteria (Phase 2 Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG.
  • Prostatic urethra involvement of NMIBC.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma. Exclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the exclusion criteria described of all patients listed above, the following

Exclusion Criteria:

  • Exclusion Criteria (All Patients):
  • Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
  • Abdomen/Pelvis
  • CT scan
  • Chest
  • chest x-ray or CT scan
  • Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects 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.
  • Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
  • Subjects who have received prior therapy with PD-1 or PD-L1 directed agents.
  • Subjects who have had any prior radiation to the prostate or pelvis.
  • Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Clinically significant cardiac diseases, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias.
  • Clinically significant resting bradycardia.
  • Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
  • Cirrhosis
  • Active Infection (includes chronic active and chronic persistent).
  • Tuberculosis
  • Hepatitis B (known positive HBV surface antigen (HbsAg). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], 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:
  • Patients with vitiligo or alopecia.
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • Patients with celiac disease controlled by diet alone.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
  • Pregnant or breast-feeding women. Women of child-bearing potential must have a negative urine or serum test ≤ 14 days prior to starting study drug.
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception or abstinence. Highly effective contraception or abstinence must be used from the time of informed consent, throughout the trial and up to 180 days after the last dose of durvalumab (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). 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).
  • Fertile males not willing to use contraception or abstinence, as stated above. Contraception or abstinence must be followed from screening through 180 days after receipt of the final dose of durvalumab therapy.
  • Subjects unwilling or unable to comply with the protocol.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Exclusion Criteria (Phase 1 Only):
  • In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients in the section listed above. Exclusion Criteria (Phase 2 Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG.
  • Prostatic urethra involvement of NMIBC.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma. Exclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to the cross-over to durvalumab portion of the Phase 2 study.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.

Contact:

  • Michael Nunley
  • 317.634.5842 Ext. 17

Location:

  • Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center
  • Baltimore Maryland 21231 United States

View trial on ClinicalTrials.gov


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


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

Intervention:

  • Drug: Enfortumab vedotin

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03219333

Sponsor: Astellas Pharma Global Development, Inc.

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 200

Study Start Date: September 20, 2017

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
  • Metastatic disease or locally advanced disease that is not resectable.
  • Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
  • Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
  • Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
  • Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
  • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

Exclusion Criteria:

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

Contact:

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

Locations:

  • Mayo Clinic Arizona
  • Scottsdale Arizona 85259 United States
  • Arizona Oncology Associates, PC - HOPE
  • Tucson Arizona 85710 United States
  • University of California Davis
  • Davis California 95616 United States
  • Keck Medical Center / University of Southern California
  • Los Angeles California 90033 United States
  • Keck Medical Center / Newport Beach
  • Newport Beach California 92663 United States
  • Kaiser Permanente Oakland
  • Oakland California 94611 United States
  • Chao Family Comprehensive Cancer Center University of California Irvine
  • Orange California 92868 United States
  • University of California Irvine - Newport
  • Orange California 92868 United States
  • Kaiser Permanente Roseville
  • Roseville California 95661 United States
  • Kaiser Permanente Sacramento
  • Sacramento California 95825 United States
  • Kaiser Permanente San Francisco
  • San Francisco California 94115 United States
  • Kaiser Permanente San Jose
  • San Jose California 95119 United States
  • Kaiser Permanente San Leandro
  • San Leandro California 94577 United States
  • Kaiser Permanente Santa Clara
  • Santa Clara California 95051 United States
  • Kaiser Permanente South San Francisco
  • South San Francisco California 94080 United States
  • Kaiser Permanente Medical Center Northern California
  • Vallejo California 94589 United States
  • Kaiser Permanente Walnut Creek
  • Walnut Creek California 94596 United States
  • Rocky Mountain Cancer Centers - Aurora
  • Aurora Colorado 80012 United States
  • Yale Cancer Center
  • New Haven Connecticut 06520 United States
  • Ocala Oncology Center
  • Ocala Florida 34471 United States
  • H. Lee Moffitt Cancer Center & Research Institute
  • Tampa Florida 33612 United States
  • University of Chicago
  • Chicago Illinois 60637-1470 United States
  • Johns Hopkins Medical Center
  • Baltimore Maryland 21231 United States
  • Maryland Oncology Hematology, P.A.
  • Silver Spring Maryland 20904 United States
  • Massachusetts General Hospital
  • Boston Massachusetts 02114 United States
  • Dana Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Karmanos Cancer Institute / Wayne State University
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • New York Oncology Hematology, P.C.
  • Albany New York 12206 United States
  • New York University (NYU) Cancer Institute
  • New York New York 10016 United States
  • Mount Sinai Medical Center
  • New York New York 10029 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10087-9049 United States
  • James P. Wilmot Cancer Center / University of Rochester Medical Center
  • Rochester New York 14642 United States
  • Duke University Medical Center
  • Durham North Carolina 27710 United States
  • Cleveland Clinic, The
  • Cleveland Ohio 44195 United States
  • James Cancer Hospital / Ohio State University
  • Columbus Ohio 43210 United States
  • Northwest Cancer Specialists, P.C.
  • Tualatin Oregon 97062 United States
  • Thomas Jefferson University
  • Philadelphia Pennsylvania 19107 United States
  • Texas Oncology - Baylor Sammons Cancer Center
  • Dallas Texas 75246 United States
  • Houston Methodist Cancer Center
  • Houston Texas 77030 United States
  • University of Virginia
  • Charlottesville Virginia 22908 United States
  • Virginia Cancer Specialists, PC
  • Fairfax Virginia 22031 United States
  • Virginia Oncology Associates
  • Norfolk Virginia 23502 United States
  • Seattle Cancer Care Alliance / University of Washington
  • Seattle Washington 98109-1023 United States
  • Site 81001
  • Aomori Japan
  • Site 81005
  • Chiba Japan
  • Site 81011
  • Fukuoka Japan
  • Site 81012
  • Fukuoka Japan
  • Site 81004
  • Ibaraki Japan
  • Site 81002
  • Iwate Japan
  • Site 81003
  • Nigata Japan
  • Site 81008
  • Osaka Japan
  • Site 81010
  • Tokushima Japan
  • Site 81006
  • Tokyo Japan
  • Site 81009
  • Yamaguchi Japan

View trial on ClinicalTrials.gov


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