Bladder Cancer Clinical Trial

A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer

Summary

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

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Full Description

This study will examine the safety and anticancer activity of enfortumab vedotin (EV) given intravenously as monotherapy and in combination with other anticancer therapies as first line (1L) and second line (2L) treatment for patients with urothelial cancer. The primary goal of the study is to determine the safety, tolerability, and efficacy of enfortumab vedotin alone and in combination with pembrolizumab and/or chemotherapy. The study will be conducted in multiple parts:

Locally advanced or metastatic urothelial cancer:

Dose escalation

Expansion

Part 1: Cohorts A and Optional B
Part 2: Cohorts D, E, and Optional F
Part 3: Cohort G.

Randomized Cohort K

EV Monotherapy Arm
EV Combination Arm

Muscle invasive bladder cancer:

Cohort H
Optional Cohort J
Cohort L

View Eligibility Criteria

Eligibility Criteria

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 mLmin and ≥30min, 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. adjuvantneoadjuvant platinum-based therapy within 12 months to randomization.

Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.

Histologically confirmed MIBC with predominant >50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.
Must be cisplatin-ineligible.
Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
ECOG performance status of 0, 1, or 2.
Anticipated life expectancy of ≥3 months.
Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
Participants must be deemed eligible for RC+PLND.

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, J, and L

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.
For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
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.
Participants with a history of another invasive malignancy within 3 years before first dose of study drug.

Study is for people with:

Bladder Cancer

Phase:

Phase 1

Estimated Enrollment:

457

Study ID:

NCT03288545

Recruitment Status:

Recruiting

Sponsor:

Astellas Pharma Global Development, Inc.

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There are 106 Locations for this study

See Locations Near You

Alaska Urological Institute
Anchorage Alaska, 99503, United States
Banner MD Anderson Cancer Center
Gilbert Arizona, 85234, United States
Mayo Clinic Arizona
Phoenix Arizona, 85054, United States
Arizona Oncology Associates, PC - HOPE
Tucson Arizona, 85710, United States
Highlands Oncology Group
Fayetteville Arkansas, 72703, United States
Tower Hematology Oncology Medical Group
Beverly Hills California, 90211, United States
UC San Diego / Moores Cancer Center
La Jolla California, 92093, United States
University of California Irvine - Newport
Orange California, 92868, United States
University of California, Davis Comprehensive Cancer Center
Sacramento California, 95817, United States
University of California at San Francisco
San Francisco California, 94134, United States
Saint Joseph Heritage Medical Group
Santa Rosa California, 95403, United States
Stanford Cancer Center / Blood & Marrow Transplant Program
Stanford California, 94305, United States
Kaiser Permanente Southern California
Woodland Hills California, 91367, United States
Rocky Mountain Cancer Centers - Aurora
Aurora Colorado, 80012, United States
University of Colorado Hospital / University of Colorado
Aurora Colorado, 80045, United States
Yale Cancer Center
New Haven Connecticut, 06520, United States
Eastern CT Hematology and Oncology Associates
Norwich Connecticut, 06360, United States
Georgetown University Medical Center
Washington District of Columbia, 20007, United States
Boca Raton Regional Hospital / Lynn Cancer Institute
Boca Raton Florida, 33486, United States
Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale Florida, 33308, United States
Mayo Clinic Florida
Jacksonville Florida, 32224, United States
University of Miami
Miami Florida, 33136, United States
Piedmont Cancer Institute
Atlanta Georgia, 30309, United States
Winship Cancer Institute / Emory University School of Medicine
Atlanta Georgia, 30322, United States
University of Chicago Medical Center
Chicago Illinois, 60637, United States
Decatur Memorial Hospital - Illinois
Decatur Illinois, 62526, United States
Northwestern Medicine Cancer Center - Kishwaukee / Kishwaukee Cancer Center
DeKalb Illinois, 60115, United States
Northwestern Medicine Cancer Center Delnor
Geneva Illinois, 60134, United States
Cardinal Bernardin Cancer Center / Loyola University Medical Center
Maywood Illinois, 60153, United States
Northwestern Medicine Cancer Center - Warrenville / Central DuPage Hospital - Cancer Care
Warrenville Illinois, 60555, United States
University of Kansas Cancer Center
Westwood Kansas, 66205, United States
Tulane University Hospital and Clinic
New Orleans Louisiana, 70112, United States
Ochsner Clinic Foundation
New Orleans Louisiana, 70121, United States
Maryland Oncology Hematology, P.A.
Silver Spring Maryland, 20904, United States
Southcoast Centers for Cancer Care - Fairhaven Site
Fairhaven Massachusetts, 02719, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor Michigan, 48109, United States
Henry Ford Health System
Detroit Michigan, 48202, United States
McLaren Greater Lansing Hospital
Lansing Michigan, 48910, United States
University of Minnesota
Minneapolis Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson Mississippi, 39213, United States
Washington University School of Medicine - Siteman Cancer Center
Saint Louis Missouri, 63110, United States
Nebraska Hematology Oncology P.C.
Lincoln Nebraska, 68506, United States
OptumCare Cancer Center
Las Vegas Nevada, 89102, United States
Memorial Sloan Kettering Cancer Center - Basking Ridge
Basking Ridge New Jersey, 07920, United States
Hackensack University Medical Center
Hackensack New Jersey, 07601, United States
Memorial Sloan Kettering Cancer Center - Monmouth
Middletown New Jersey, 07748, United States
Memorial Sloan Kettering Cancer Center - Bergen
Montvale New Jersey, 07645, United States
University of New Mexico Cancer Center
Albuquerque New Mexico, 87106, United States
New York Oncology Hematology, P.C.
Albany New York, 12206, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Memorial Sloan Kettering Cancer Center - Commack
Commack New York, 11725, United States
Memorial Sloan Kettering Cancer Center - Westchester
Harrison New York, 10604, United States
Northwell Cancer Center / Monter Cancer Center
Lake Success New York, 11042, United States
NYU Winthrop Hospital
Mineola New York, 11501, United States
New York University (NYU) Cancer Institute
New York New York, 10016, United States
Weill Cornell Medical College
New York New York, 10065, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10087, United States
University of Rochester Medical Center
Rochester New York, 14642, United States
Memorial Sloan Kettering Cancer Center - Nassau
Uniondale New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
Chapel Hill North Carolina, 27599, United States
Levine Cancer Institute
Charlotte North Carolina, 28204, United States
Duke University Medical Center
Durham North Carolina, 27710, United States
Vidant Medical Center
Greenville North Carolina, 27834, United States
Gabrail Cancer Center Research, LLC
Canton Ohio, 44718, United States
Case Western Reserve University / University Hospitals Case Medical Center
Cleveland Ohio, 44106, United States
Toledo Clinic Cancer Center
Toledo Ohio, 43623, United States
CMOH Broomall
Broomall Pennsylvania, 19008, United States
Penn State Milton S. Hershey Medical Center
Hershey Pennsylvania, 17033, United States
Fox Chase Cancer Center
Philadelphia Pennsylvania, 19111, United States
Allegheny General Hospital
Pittsburgh Pennsylvania, 15212, United States
Medical University of South Carolina/Hollings Cancer Center
Charleston South Carolina, 29425, United States
Saint Francis Hospital Cancer Center
Greenville South Carolina, 29607, United States
Carolina Urologic Research Center
Myrtle Beach South Carolina, 29572, United States
Sarah Cannon Research Institute
Chattanooga Tennessee, 37404, United States
Tennessee Oncology / Sarah Cannon Research Institute
Nashville Tennessee, 37203, United States
Texas Oncology - Fort Worth Cancer Center
Fort Worth Texas, 76104, United States
University of Texas Health Science Center at San Antonio
San Antonio Texas, 78229, United States
Texas Oncology - Tyler
Tyler Texas, 75702, United States
Utah Cancer Specialists
Salt Lake City Utah, 84106, United States
University of Virginia
Charlottesville Virginia, 22903, United States
Virginia Oncology Associates - Norfolk
Norfolk Virginia, 23502, United States
Medical Oncology Associates
Spokane Washington, 99208, United States
Medical College of Wisconsin (Milwaukee)
Milwaukee Wisconsin, 53226, United States
Site CA11008
East Brampton Ontario, L6R 3, Canada
Site CA11011
Kingston Ontario, K7L 2, Canada
Site CA11001
Toronto Ontario, M5G 2, Canada
Site CA11005
Montreal Quebec, H3T1E, Canada
Site CA11013
Montreal Quebec, H4A3J, Canada
Site CA11002
Sherbrooke Quebec, J1H 5, Canada
Site FR33008
Bordeaux , 33000, France
Site FR33005
Dijon , 21000, France
Site FR33003
Lyon , 69008, France
Site FR33004
Marseilles , 13273, France
Site FR33010
Moselle , 54519, France
Site FR33002
Nice Cedex , 06189, France
Site FR33006
Pierre-Benite , 69310, France
Site FR33001
Strasbourg , 67200, France
Site IT39002
Terni , 05100, Italy
Site PR78701
Rio Piedras , 00935, Puerto Rico
Site ES34006
Barcelona , 08041, Spain
Site ES34008
Madrid , 28033, Spain
Site ES34001
Madrid , 28034, Spain
Site ES34012
Madrid , 28041, Spain
Site ES34007
Pamplona , 31008, Spain
Site ES34005
Sabadell , 08208, Spain
Site ES34004
Santander , 39008, Spain

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 1

Estimated Enrollment:

457

Study ID:

NCT03288545

Recruitment Status:

Recruiting

Sponsor:


Astellas Pharma Global Development, Inc.

How clear is this clinincal trial information?

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