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Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02563002
First received: September 28, 2015
Last updated: June 20, 2017
Last verified: June 2017
  Purpose
In this study, participants with MSI-H or dMMR advanced colorectal carcinoma will be randomly assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for the treatment of advanced colorectal carcinoma. The primary study hypothesis is that pembrolizumab will prolong progression-free survival (PFS) compared to current SOC chemotherapy.

Condition Intervention Phase
Colorectal Carcinoma Drug: mFOLFOX6 Drug: FOLFIRI Biological: pembrolizumab Biological: bevacizumab Biological: cetuximab Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase III Study of Pembrolizumab (MK-3475) vs. Chemotherapy in Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (KEYNOTE-177)

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 57 months ]

Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: Up to 57 months ]
  • Overall Survival (OS) [ Time Frame: Up to 57 months ]

Estimated Enrollment: 270
Actual Study Start Date: November 30, 2015
Estimated Study Completion Date: September 18, 2019
Estimated Primary Completion Date: August 15, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years)
Biological: pembrolizumab
Active Comparator: Standard of Care
Per Investigator choice, participants receive 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6 + bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6 + cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI + bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI + cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle
Drug: mFOLFOX6
Regimen consists of oxaliplatin 85 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle
Drug: FOLFIRI
Regimen consists of irinotecan 180 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-FU 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle
Biological: bevacizumab Biological: cetuximab

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Locally confirmed dMMR or MSI-H stage IV colorectal carcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Measurable disease
  • Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of SOC therapy or 120 days after the last pembrolizumab dose
  • Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of SOC therapy or 120 days after the last pembrolizumab dose
  • Adequate organ function

Exclusion Criteria:

  • Has received prior systemic therapy for Stage IV colorectal cancer. May have received prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least 6 months prior to randomization on this study
  • Currently participating and receiving treatment in another study, or participated in a study of an investigational agent and received treatment, or used an investigational device within 4 weeks of randomization
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization on this study
  • Radiation therapy within 4 weeks prior to randomization on this study and not recovered to baseline from adverse events due to radiation therapy
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization on this study
  • Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.)
  • Another malignancy that is progressing or requires active treatment with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma
  • Received a live vaccine within 30 days of planned start of study medication
  • Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
  • Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of SOC or 120 days after the last dose of pembrolizumab
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02563002

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 80 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Additional Information:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02563002     History of Changes
Other Study ID Numbers: 3475-177
2015-002024-89 ( EudraCT Number )
163238 ( Registry Identifier: JAPIC-CTI )
Study First Received: September 28, 2015
Last Updated: June 20, 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PDL1
PD-L1

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Microsatellite Instability
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Genomic Instability
Pathologic Processes
Bevacizumab
Pembrolizumab
Cetuximab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 22, 2017