Overview

This trial is active, not recruiting.

Condition urothelial cancer
Treatments pembrolizumab, paclitaxel, vinflunine, docetaxel
Phase phase 3
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date October 2014
End date May 2017
Trial size 542 participants
Trial identifier NCT02256436, 152903, 2014-002009-40, 3475-045

Summary

Participants with metastatic or locally advanced/unresectable urothelial cancer that has recurred or progressed following platinum-based chemotherapy will be randomly assigned to receive pembrolizumab or Investigator's choice of paclitaxel, docetaxel, or vinflunine. The primary study hypotheses are that pembrolizumab will prolong overall survival (OS) and progression free survival (PFS) compared to paclitaxel, docetaxel, or vinflunine.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W)
pembrolizumab MK-3475
IV infusion
(Active Comparator)
Participants receive paclitaxel 175 mg/m^2 IV, docetaxel 75 mg/m^2 IV, or vinflunine 320 mg/m^2 IV, on Day 1 Q3W
paclitaxel
IV infusion
vinflunine
IV infusion
docetaxel
IV infusion

Primary Outcomes

Measure
Overall survival (OS) - All Participants
time frame: Up to 30 months
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) - All Participants
time frame: Up to 30 months
OS - Participants with strongly PD-L1 positive tumors
time frame: Up to 30 months
PFS per RECIST 1.1 - Participants with strongly PD-L1 positive tumors
time frame: Up to 30 months
OS - Participants with PD-L1 positive tumors
time frame: Up to 30 months
PFS per RECIST 1.1 - Participants with PD-L1 positive tumors
time frame: Up to 30 months

Secondary Outcomes

Measure
Objective response rate (ORR) per RECIST 1.1
time frame: Up to 30 months
PFS per modified RECIST 1.1
time frame: Up to 30 months
ORR per modified RECIST 1.1
time frame: Up to 30 months
Number of participants who experience an adverse event (AE)
time frame: Up to 31 months
Number of participants who discontinue study drug due to an AE
time frame: Up to 30 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria: - Histologically- or cytologically-confirmed diagnosis of urothelial cancer of the renal pelvis, ureter, bladder, or urethra, that is transitional cell or mixed transitional/non-transitional (predominantly transitional) cell type - Progression or recurrence of urothelial cancer following a first-line platinum-containing regimen (e.g cisplatin, carboplatin) for metastatic or inoperable locally advanced disease; or adjuvant platinum-based therapy following cystectomy for localized muscle-invasive urothelial cancer with recurrence/progression <=12 months following completion of therapy; or neoadjuvant platinum-containing therapy prior to cystectomy for localized muscle-invasive urothelial cancer with recurrence <=12 months following completion of therapy - No more than 2 prior lines of systemic chemotherapy for metastatic urothelial cancer - Able to provide tissue for biomarker analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated - Measureable disease - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Adequate organ function - Female participants of childbearing potential have a negative urine or serum pregnancy test; or are surgically sterile, or willing to use 2 acceptable methods of birth control, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of pembrolizumab or 180 days after the last dose of paclitaxel, docetaxel, or vinflunine - Male participants must be willing to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of pembrolizumab or 180 days after the last dose of paclitaxel, docetaxel, or vinflunine Exclusion criteria: - Urothelial cancer that is suitable for local therapy administered with curative intent - Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of trial medication - Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication - Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events due to agents administered more than 4 weeks earlier - Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of study Day 1 or not recovered from adverse events due to a previously administered agent - Prior therapy with all choices of active comparator - Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cancer; or prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer that is Stage T2N0M0 or lower, Gleason score<= 6, or prostatic-specific antigen (PSA) undetectable - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents - Active cardiac disease - Evidence of interstitial lung disease or active non-infectious pneumonitis - Active infection requiring systemic therapy - History of severe hypersensitivity reaction to paclitaxel, docetaxel, or to other drugs formulated with polysorbate 80 or polyoxyethylated castor oil, or to vinflunine or other vinca alkaloids - Requires ongoing therapy with a medication that is a strong inhibitor or inducer of the cytochrome 3A4 (CYP3A4) enzymes - Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of paclitaxel, docetaxel, or vinflunine - Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor - Human immunodeficiency virus (HIV) - Active hepatitis B or hepatitis C - Received a live virus vaccine within 30 days of planned start of trial treatment

Additional Information

Official title A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..