Clinical trial NCT04126733: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-10-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator
timeFrame: Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
measure: Disease Control Rate (DCR) at 8 and 16 Weeks
timeFrame: At 8, 16, 24, 32 and 40 weeks
measure: Progression-free Survival (PFS)
timeFrame: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
measure: Overall Survival (OS)
timeFrame: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
timeFrame: 30 days after last dose of regorafenib and 100 days after last dose of nivolumab until study completion (up to 30 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health South Florida
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, PA
state: Minnesota
city: Papillion
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Albany
country: United States
facility: New York Oncology Hematology. P.C.
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Arlington
country: United States
facility: Texas Oncology-Arlington North
state: Texas
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Sherman
country: United States
facility: Texas Oncology-Sherman
state: Texas
city: Newport News
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, PC
state: Washington
Study officials:
References: