Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Participants With Advanced Melanoma (P08719/KEYNOTE-002)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01704287
First received: October 8, 2012
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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. 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 cross-over to treatment with pembrolizumab provided they meet protocol-specified requirements for cross-over.


Condition Intervention Phase
Malignant Melanoma
Drug: Pembrolizumab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Dacarbazine
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Phase II Study of MK-3475 Versus Chemotherapy in Patients With Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression-free-survival (PFS) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  • Response Duration [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 510
Study Start Date: November 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab Low dose Drug: Pembrolizumab
Pembrolizumab, intravenously (IV) at a dose assigned at randomization
Experimental: Pembrolizumab Higher Dose Drug: Pembrolizumab
Pembrolizumab, intravenously (IV) at a dose assigned at randomization
Active Comparator: Investigator-Choice Chemotherapy
Participants on this arm will receive one of 4 possible chemotherapy regimens decided at the treating institution (carboplatin + paclitaxel, paclitaxel alone, dacarbazine, or temozolomide).
Drug: Carboplatin
Carboplatin per institutional standard.
Drug: Paclitaxel
Paclitaxel per institutional standard.
Drug: Dacarbazine
Dacarbazine per institutional standard.
Other Name: DTIC
Drug: Temozolomide
Temozolomide per institutional standard.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 Performance Status of 0 or 1

Exclusion criteria:

  • Chemotherapy, radiation therapy, or biological therapy within four weeks prior to the first dose of study drug, or not recovered from the AEs due to cancer therapies administered more than four 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01704287     History of Changes
Other Study ID Numbers: P08719, MK-3475-002
Study First Received: October 8, 2012
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
PD-1
PD1

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Paclitaxel
Temozolomide
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 22, 2014