Overview

This trial is active, not recruiting.

Condition malignant melanoma
Treatments pembrolizumab, carboplatin, paclitaxel, dacarbazine, temozolomide
Phase phase 2
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date November 2012
End date November 2015
Trial size 540 participants
Trial identifier NCT01704287, MK-3475-002, P08719

Summary

This study is being done to compare survival using pembrolizumab (MK-3475) or standard chemotherapy for participants with advanced melanoma (MEL) who have progressed after prior therapy.

Participants will be randomized to receive either low dose pembrolizumab, higher dose pembrolizumab or Investigator-choice chemotherapy. The pembrolizumab dose will be blinded to Investigators and participants. With Amendment 03, all ongoing pembrolizumab participants will be treated with open-label, fixed dose pembrolizumab 200 mg every 3 weeks (Q3W), instead of weight-based dosing of pembrolizumab.

The randomization to either pembrolizumab or Investigator choice chemotherapy will be conducted in open-label fashion. The four standard chemotherapy choices are carboplatin + paclitaxel, paclitaxel alone, dacarbazine, or temozolomide. Participants on standard chemotherapy who experience disease progression may be eligible to crossover to treatment with pembrolizumab provided they meet protocol-specified requirements for crossover. Crossover participants will be treated with open-label, fixed dose pembrolizumab 200 mg Q3W.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
This arm was discontinued with Amendment 03. All pembrolizumab participants will be treated with fixed dose pembrolizumab 200 mg, intravenously (IV) Q3W.
pembrolizumab MK-3475
IV infusion
(Experimental)
This arm was discontinued with Amendment 03. All pembrolizumab participants will be treated with fixed dose pembrolizumab 200 mg IV Q3W.
pembrolizumab MK-3475
IV infusion
(Active Comparator)
Participants receive one of 4 possible chemotherapy regimens decided at the treating institution (carboplatin + paclitaxel, paclitaxel alone, dacarbazine, or temozolomide).
carboplatin PARAPLATIN®
Carboplatin per institutional standard.
paclitaxel TAXOL®
Paclitaxel per institutional standard.
dacarbazine DTIC
Dacarbazine per institutional standard.
temozolomide TEMODAR®
Temozolomide per institutional standard.
(Experimental)
All pembrolizumab and crossover participants will be treated with fixed dose pembrolizumab 200 mg Q3W. Participants receive pembrolizumab 200 mg IV Q3W.
pembrolizumab MK-3475
IV infusion

Primary Outcomes

Measure
Progression-free Survival (PFS)
time frame: Up to 24 months
Overall Survival (OS)
time frame: Up to 24 months

Secondary Outcomes

Measure
Overall Response Rate (ORR)
time frame: Up to 24 months
Duration of Response (DOR)
time frame: Up to 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic MEL not amenable to local therapy - Participants must be refractory to ipilimumab - Participants with BRAF gene mutant melanoma must have had a prior treatment regimen that included vemurafenib, dabrafenib, or an approved BRAF gene and/or mitogen-activated protein kinase (MEK) protein inhibitor - Must consent to allow correlative studies; must provide a newly obtained tissue/biopsy specimen (or specimen obtained within 60 days of consenting) - Radiographically measurable disease - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Exclusion criteria: - Chemotherapy, radiation therapy, or biological therapy within 4 weeks prior to the first dose of study drug, or not recovered from the adverse events due to cancer therapies administered more than 4 weeks earlier - Disease progression within 24 weeks of last dose of ipilimumab - Participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug - Expected to require any other form of systemic or localized antineoplastic therapy while on study - Chronic systemic steroid therapy within two weeks before the planned date for first dose randomized treatment or on any other form of immunosuppressive medication - Known history of any other than the current malignancy excepting adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, breast cancer, or other in situ cancers - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents - Prior treatment with any other anti-programmed cell death (PD) agent - Active infection requiring systemic therapy - Known history of Human Immunodeficiency Virus (HIV) - Active Hepatitis B or Hepatitis C - Regular user (including recreational use of) illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol) - Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study

Additional Information

Official title Randomized, Phase II Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Patients With Advanced Melanoma (KEYNOTE 002)
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..