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.
Verified June 2017 by Merck Sharp & Dohme Corp.
Sponsor:
Merck Sharp & Dohme Corp.
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
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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
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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
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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 July 17, 2017


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