Study on the Effectiveness and Safety of the Combination of the Two Drugs Regorafenib and Nivolumab in Patients With Colorectal Cancer (Cancer of the Colon or Rectum Classified as Proficient Mismatch Repair and Microsatellite Stable)
An Open-label, Single-arm, Phase II Study of Regorafenib and Nivolumab in Patients With Mismatch Repair-Proficient (pMMR)/Microsatellite Stable (MSS) Colorectal Cancer (CRC)
1 other identifier
interventional
70
1 country
15
Brief Summary
The purpose of this study is to learn if combination of the two drugs regorafenib and nivolumab is an effective treatment for pMMR - MSS colorectal cancer, a special type of cancer of the colon or rectum (pMMR stands for proficient Mismatch Repair; MSS stands for Microsatellite Stable) and whether it is safe for patients. Regorafenib works by blocking several different proteins involved in tumor growth. Nivolumab is an immunotherapy drug encouraging the body's own immune system to attack cancer cells. Both drugs have been approved, but not for how they are being used as combination therapy in this study. Brand name of regorafenib is Stivarga; brand name of nivolumab is Opdivo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 colorectal-cancer
Started Oct 2019
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
October 11, 2019
CompletedStudy Start
First participant enrolled
October 14, 2019
CompletedFirst Posted
Study publicly available on registry
October 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2020
CompletedResults Posted
Study results publicly available
December 14, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 28, 2022
CompletedJuly 18, 2023
June 1, 2023
1.1 years
October 11, 2019
November 3, 2021
June 25, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator
ORR was defined as the percentage of participants with overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)
Secondary Outcomes (5)
Duration of Response (DOR)
Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
Disease Control Rate (DCR) at 8 and 16 Weeks
At 8, 16, 24, 32 and 40 weeks
Progression-free Survival (PFS)
Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
Overall Survival (OS)
Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
30 days after last dose of regorafenib and 100 days after last dose of nivolumab until study completion (up to 30 months)
Study Arms (1)
Regorafenib + Nivolumab
EXPERIMENTALInterventions
Regorafenib administered as oral tablets given every day for 3 weeks of each 28 days treatment cycle (i.e., 3 weeks on, 1 week off)
Eligibility Criteria
You may qualify if:
- Histological or cytological confirmed advanced, metastatic, or progressive pMMR/MSS adenocarcinoma of colon or rectum
- Participant must have progressed or be intolerant to prior systemic chemotherapy including fluoropyrimidines, irinotecan, oxaliplatin, anti-vascular endothelial growth factor (VEGF) therapy, and, if extended rat sarcoma viral oncogene homolog (RAS) wild type, an anti-epidermal growth factor receptor (EGFR) therapy. Exceptions may apply
- Participants must have adequate organ and marrow function defined by protocol-specified laboratory tests
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Measurable disease as determined by response evaluation criteria in solid tumors (RECIST) v1.1
- Provision of recently obtained tumor tissue as per protocol specified requirement
- Anticipated life expectancy greater than 3 months
- Be able to swallow and absorb oral tablets
You may not qualify if:
- Participants with Mismatch repair deficient (dMMR) / microsatellite instable-high (MSI-H) colorectal cancer
- Prior therapy with regorafenib, anti-programmed cell death protein 1 (PD-1), programmed cell death protein 1 ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of immunotherapy to treat cancer
- Presence of active central nervous system (CNS) metastases; participants with stable CNS disease or previously treated lesions are eligible for study entry
- Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 mmHg despite optimal medical management
- Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study medication. Active pulmonary emboli or deep vein thrombosis that are significant or not adequately controlled on anticoagulation regimen
- Any hemorrhage or bleeding event ≥ National Cancer Institute - Common terminology criteria for adverse events (NCI-CTCAE) Grade 3 within 28 days prior to the start of study medication
- Participants with an active, known or suspected autoimmune disease
- History of interstitial lung disease or pneumonitis
- Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
- Bristol-Myers Squibbcollaborator
Study Sites (15)
City of Hope National Medical Center
Duarte, California, 91010, United States
Rocky Mountain Cancer Centers
Denver, Colorado, 80218, United States
Miami Cancer Institute at Baptist Health South Florida
Miami, Florida, 33176, United States
Illinois Cancer Specialists
Arlington Heights, Illinois, 60005, United States
Minnesota Oncology Hematology, PA
Minneapolis, Minnesota, 55404, United States
Nebraska Cancer Specialists
Papillion, Nebraska, 68046, United States
New York Oncology Hematology. P.C.
Albany, New York, 12206, United States
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401, United States
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203, United States
Texas Oncology-Arlington North
Arlington, Texas, 76012, United States
Baylor Charles A. Sammons Cancer Center at Dallas
Dallas, Texas, 75246, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Oncology-Sherman
Sherman, Texas, 75090, United States
Virginia Oncology Associates
Newport News, Virginia, 23606, United States
Northwest Cancer Specialists, PC
Vancouver, Washington, 98684, United States
Related Publications (1)
Fakih M, Raghav KPS, Chang DZ, Larson T, Cohn AL, Huyck TK, Cosgrove D, Fiorillo JA, Tam R, D'Adamo D, Sharma N, Brennan BJ, Wang YA, Coppieters S, Zebger-Gong H, Weispfenning A, Seidel H, Ploeger BA, Mueller U, Oliveira CSV, Paulson AS. Regorafenib plus nivolumab in patients with mismatch repair-proficient/microsatellite stable metastatic colorectal cancer: a single-arm, open-label, multicentre phase 2 study. EClinicalMedicine. 2023 Apr 6;58:101917. doi: 10.1016/j.eclinm.2023.101917. eCollection 2023 Apr.
PMID: 37090438DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Preliminary efficacy assessment suggested that the study would not meet its primary efficacy endpoint, therefore the study was stopped.
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- Bayer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 11, 2019
First Posted
October 15, 2019
Study Start
October 14, 2019
Primary Completion
November 11, 2020
Study Completion
March 28, 2022
Last Updated
July 18, 2023
Results First Posted
December 14, 2021
Record last verified: 2023-06