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Study of Pembrolizumab With or Without Platinum-based Combination Chemotherapy Versus Chemotherapy Alone in Urothelial Carcinoma (MK-3475-361/KEYNOTE-361)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02853305
Recruitment Status : Active, not recruiting
First Posted : August 2, 2016
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE July 29, 2016
First Posted Date  ICMJE August 2, 2016
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE September 15, 2016
Actual Primary Completion Date May 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • 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 ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
  • Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to approximately 24 months ]
  • Objective Response Rate (ORR) Using RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 24 months ]
  • Disease Control Rate (DCR) Using RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 24 months ]
  • PFS Using RECIST 1.1 as Assessed by BICR at Milestone Timepoints [ Time Frame: At 6, 12, 18 and 24 months ]
  • Duration of Response (DOR) Using RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 24 months ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
  • Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to approximately 24 months ]
  • Objective Response Rate (ORR) Using RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 24 months ]
  • Disease Control Rate (DCR) Using RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 24 months ]
  • PFS Using RECIST 1.1 as Assessed by BICR at Milestone Timepoints [ Time Frame: At 6, 12, 18 and 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab With or Without Platinum-based Combination Chemotherapy Versus Chemotherapy Alone in Urothelial Carcinoma (MK-3475-361/KEYNOTE-361)
Official Title  ICMJE 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
Brief Summary

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%]).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma Associated 1 RNA, Human
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Cisplatin
    IV infusion
  • Drug: Carboplatin
    IV infusion
  • Drug: Gemcitabine
    IV infusion
Study Arms  ICMJE
  • Experimental: Pembrolizumab
    Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for a maximum of 35 doses.
    Intervention: Biological: Pembrolizumab
  • Experimental: Pembrolizumab+Chemotherapy
    Participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for a maximum of 35 doses PLUS EITHER cisplatin 70 mg/m^2 IV on Day 1 (or Day 2 if required per local guidelines) of each 3-week cycle + gemcitabine IV infusion 1,000 mg/m^2 on Day 1 and Day 8 of each 3-week cycle, OR carboplatin area under the curve 5 (AUC 5) (or AUC 4.5 if required per local guidelines) IV on Day 1 (or Day 2 if required per local guidelines) of each 3-week cycle + gemcitabine 1,000 mg/m^2 IV on Day 1 and Day 8 of each 3-week cycle.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Gemcitabine
  • Active Comparator: Chemotherapy
    Participants receive EITHER cisplatin 70 mg/m^2 IV on Day 1 (or Day 2 if required per local guidelines) of each 3-week cycle + gemcitabine IV infusion 1,000 mg/m^2 on Day 1 and Day 8 of each 3-week cycle OR carboplatin AUC 5 (or AUC 4.5 if required per local guidelines) IV on Day 1 (or Day 2 if required per local guidelines) of each 3-week cycle + gemcitabine 1,000 mg/m^2 IV on Day 1 and Day 8 of each 3-week cycle.
    Interventions:
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 19, 2020)
1010
Original Estimated Enrollment  ICMJE
 (submitted: July 29, 2016)
990
Estimated Study Completion Date  ICMJE May 31, 2022
Actual Primary Completion Date May 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Belgium,   Brazil,   Canada,   Chile,   France,   Germany,   Hungary,   Ireland,   Israel,   Japan,   Korea, Republic of,   Netherlands,   Russian Federation,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02853305
Other Study ID Numbers  ICMJE 3475-361
2015-005731-41 ( EudraCT Number )
163458 ( Registry Identifier: JAPIC-CTI )
MK-3475-361 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP