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)

Phase 2

Completed

Conditions: Colorectal Cancer

Interventions: Drug: Regorafenib (Stivarga, BAY73-4506)
Biological: Nivolumab (Opdivo)

Registration Number: NCT04126733

Lead Sponsor: Bayer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

Inclusion Criteria

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

Exclusion Criteria

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
Other protocol defined inclusion/exclusion criteria could apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Regorafenib + Nivolumab	Regorafenib (Stivarga, BAY73-4506)	-
Regorafenib + Nivolumab	Nivolumab (Opdivo)	-

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator	Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)	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.

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate (DCR) at 8 and 16 Weeks	At 8, 16, 24, 32 and 40 weeks	DCR was defined as the percentage of participants with tumor response of complete response (CR), partial response (PR) or stable disease (SD). 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. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.
Overall Survival (OS)	Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)	OS was defined as time from first dose of the study treatment to death. For patients who did not die, OS was censored at the last time point at which the survival status was known to be alive.
Duration of Response (DOR)	Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)	DOR was defined for responders only as the time from first documentation of response (i.e. CR or PR) until disease progression or death (if death without documented disease progression). 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.
Progression-free Survival (PFS)	Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)	PFS was the time from first dose of study medication to disease progression or death, whichever was earlier.
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)	TEAEs were started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab.). TEAEs were summarized by system organ class (SOC) and preferred term, severity (based on CTCAE v5 grades). Laboratory data considered as AE were graded according to CTCAE v5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

Trial Locations

Locations (15): Northwest Cancer Specialists, PC
🇺🇸
Vancouver, Washington, United States
Minnesota Oncology Hematology, PA
🇺🇸
Minneapolis, Minnesota, United States
Baylor Charles A. Sammons Cancer Center at Dallas
🇺🇸
Dallas, Texas, United States
Miami Cancer Institute at Baptist Health South Florida
🇺🇸
Miami, Florida, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸
Eugene, Oregon, United States
Texas Oncology-Arlington North
🇺🇸
Arlington, Texas, United States
Texas Oncology-Sherman
🇺🇸
Sherman, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Rocky Mountain Cancer Centers
🇺🇸
Denver, Colorado, United States
Illinois Cancer Specialists
🇺🇸
Arlington Heights, Illinois, United States
Nebraska Cancer Specialists
🇺🇸
Papillion, Nebraska, United States
New York Oncology Hematology. P.C.
🇺🇸
Albany, New York, United States
Sarah Cannon Cancer Center
🇺🇸
Nashville, Tennessee, United States
Virginia Oncology Associates
🇺🇸
Newport News, Virginia, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States