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


Condition: Urothelial Carcinoma Associated 1 RNA, Human

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02853305

Sponsor: Merck Sharp & Dohme Corp.

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 990

Study Start Date: September 15, 2016

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Contact:

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

Locations:

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

View trial on ClinicalTrials.gov


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