Study of Pembrolizumab With Pemetrexed and Oxaliplatin in Chemo-Refractory Metastatic Colorectal Cancer Patients
A Phase IB Study of Pembrolizumab in Combination With Pemetrexed and Oxaliplatin in Patients With Chemo-Refractory Metastatic Colorectal Cancer
1 other identifier
interventional
33
1 country
15
Brief Summary
This is a Phase Ib study to evaluate the safety and preliminary anti-tumor activity of pembrolizumab in combination with pemetrexed with or without oxaliplatin in patients with chemo-refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC) without any further standard treatment options.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2019
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 31, 2018
CompletedFirst Posted
Study publicly available on registry
August 13, 2018
CompletedStudy Start
First participant enrolled
May 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2022
CompletedJune 10, 2022
June 1, 2022
2.5 years
July 31, 2018
June 8, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Objective Response Rate to pembrolizumab plus pemetrexed
Objective Response Rate using modified RECIST 1.1.
From initiation of pembrolizumab and pemetrexed until disease progression, intolerable toxicity, or completion of 35 cycles (each cycle is 21 days), approximately 2 years.
Objective Response Rate to pembrolizumab and pemetrexed plus oxaliplatin
Objective Response Rate using modified RECIST 1.1.
From initiation of pembrolizumab and pemetrexed plus oxaliplatin until disease progression intolerable toxicity, or completion of 35 cycles (each cycle is 21 days), approximately 2 years.
Secondary Outcomes (5)
Frequency of Adverse Events
From begining of study therapy until disease progression, intolerable toxicity, or completion of 35 cycles (each cycle is 21 days), approximately 2 years.
Frequency of Adverse Events
From begining of study therapy until disease progression, intolerable toxicity, or completion of 35 cycles (each cycle is 21 days), approximately 2 years.
Clinical Benefit Rate
From initiation of study therapy until disease progression, approximately 2 years.
Progression-Free Survival
From initiation of study therapy until disease progression, approximately 2 years.
Overall Survival
Time of study entry through 1 year.
Study Arms (2)
Cohort 1
EXPERIMENTALPembrolizumab + Pemetrexed every 21 days. Folic Acid 5 days prior to first dose of pemetrexed and daily including 21 days after last dose of pemetrexed. Dexamethasone twice daily on the day before, the day of, and the day after each dose of pemetrexed. Vitamin B-12 7 days prior to first dose of pemetrexed, every 9 weeks, continue until 3 weeks after last dose of pemetrexed.
Cohort 2
EXPERIMENTALPembrolizumab + Pemetrexed + Oxaliplatin every 21 days. Folic Acid 5 days prior to first dose of pemetrexed and daily including 21 days after last dose of pemetrexed. Dexamethasone twice daily on the day before, the day of, and the day after each dose of pemetrexed. Vitamin B-12 7 days prior to first dose of pemetrexed, every 9 weeks, continue until 3 weeks after last dose of pemetrexed.
Interventions
Pembrolizumab 200 mg IV on Day 1 of each 21 day cycle until maximum of 35 cycles.
Pemetrexed 500 mg/m2 IV on Day 1 of each 21 day cycle until maximum of 35 cycles.
Oxaliplatin-Dose level1: 85 mg/m2 IV on Day 1 of each 21 day cycle until a maximum of 35 cycles or until discontinued due to patient election, toxicity, disease progression. Dose level 2: 120 mg/m2 IV on Day 1 of each 21 day cycle until a maximum of 35 cycles or until discontinued due to patient election, toxicity, disease progression. The MTD dose of oxaliplatin in the study combination of Cohort 2 will be the recommended Phase II dose (RP2D) for the cohort expansion.
Dexamethasone-4 mg by mouth twice daily on: the day before, the day of, and the day after each dose of pemetrexed.
Folic Acid-400 micrograms by mouth daily starting 5 days prior to first dose of pemetrexed and continue daily to include 21 days after the last dose of pemetrexed.
1000 micrograms administered intramuscularly 7 days prior to the first dose of pemetrexed, every 9 weeks, and should continue until 3 weeks after the last dose of pemetrexed.
Eligibility Criteria
You may qualify if:
- The patient must have consented to participate and, prior to beginning specific study procedures, must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for study treatment.
- The ECOG performance status must be 0 or 1.
- There must be histologic or cytologic confirmation of a diagnosis of microsatellite stable (MSS) colorectal adenocarcinoma using CLIA certified IHC or PCR-based MSI testing.
- Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy.
- There must be documentation by PET/CT scan, CT scan, or MRI that the patient has evidence of measurable metastatic disease per RECIST 1.1.
- Patients must have had prior treatment for metastatic or unresectable for cure of colorectal cancer with standard chemotherapy including fluoropyrimidine-, oxaliplatin- and irinotecan- based chemotherapy, and if RAS wild-type, an anti-EGFR therapy.
- At the time of study entry, blood counts performed within 2 weeks prior to study entry must meet the following criteria:
- ANC must be greater than or equal to 1500/mm3;
- Platelet count must be greater than or equal to 100,000/mm3; and
- Hemoglobin must be greater than or equal to 9 g/dL.
- The following criteria for evidence of adequate hepatic function performed within 2 weeks prior to study entry must be met:
- Total bilirubin must be less than or equal to 1.5 x ULN.
- AST and ALT must be less than or equal to 2.5 x ULN for the lab except in the presence of known hepatic metastasis, wherein transaminases may be up to 5 x ULN.
- Alkaline phosphatase must be less than or equal to 3 x ULN for the lab.
- International normalized ratio of prothrombin time must be less than or equal to 1.5 times the ULN. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history. For laboratories that do not report an ULN for the INR assay, use less than or equal to 1.2 as the value for the ULN.
- +6 more criteria
You may not qualify if:
- Diagnosis of anal or small bowel carcinoma.
- Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy.
- Use and/or receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal anti-bodies) or radiation therapy within 4 weeks prior to receiving first dose of study therapy.
- Prior monoclonal antibody therapy within 4 weeks prior to first dose of FC-10 study therapy or who has not recovered (i.e., less than or equal to grade 1 or at baseline) from adverse events due to a previously administered agent.
- Neuropathy greater than grade 1.
- 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 steroids or immunosuppressive agents. Note: steroid use is permitted only as indicated per protocol.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study therapy. Administration of killed vaccines is allowed.
- Known history of hepatitis B or hepatitis C.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment.
- Active infection or chronic infection requiring systemic therapy.
- Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency-related (AIDS) illnesses.
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) is not allowed.
- History of allogeneic organ transplantation.
- Any of the following cardiac conditions:
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NSABP Foundation Inclead
- Merck Sharp & Dohme LLCcollaborator
- Eli Lilly and Companycollaborator
Study Sites (15)
UF Health Davis Cancer Pavilion & Shands Medical Plaza
Gainesville, Florida, 32608, United States
Cancer Care Specialists of Central Illinois
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Cancer Care Specialists of Central IL-Swansea
Swansea, Illinois, 062226, United States
University of Michigan-Oncology
Ann Arbor, Michigan, 48109, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
University of Michigan-Brighton Center for Specialty Care
Brighton, Michigan, 48116, United States
Minnesota Oncology-Minneapolis
Minneapolis, Minnesota, 55404, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
HealthPartners Riverside Clinic
Minneapolis, Minnesota, 55454, United States
Hubert H. Humphrey Cancer Center
Robbinsdale, Minnesota, 55422, United States
Metro Minnesota Community Oncology Research Consortium-MMCORC
Saint Louis Park, Minnesota, 55416, United States
Thomas Jefferson University Hospital-Sidney Kimmel Cancer Network
Philadelphia, Pennsylvania, 19107, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Norman Wolmark, MD
NSABP Foundation Inc
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 31, 2018
First Posted
August 13, 2018
Study Start
May 15, 2019
Primary Completion
October 31, 2021
Study Completion
November 1, 2022
Last Updated
June 10, 2022
Record last verified: 2022-06