check_circleStudy Completed

Colorectal Cancer

Bayer Identifier:

20975

ClinicalTrials.gov Identifier:

NCT04126733

EudraCT Number:

Not Available

EU CT Number:

Not Available
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)

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - 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
  • - 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

Trial summary

Enrollment Goal
70
Trial Dates
October 2019 - March 2022
Phase
Phase 2
Could I Receive a placebo
No
Products
Regorafenib+Nivolumab
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
City of Hope National Medical CenterDuarte, 91010, United States
Completed
Minnesota Oncology Hematology, PAMinneapolis, 55404, United States
Completed
Sarah Cannon Cancer CenterNashville, 37203, United States
Completed
New York Oncology Hematology. P.C.Albany, 12206, United States
Completed
Northwest Cancer Specialists, PCVancouver, 98684, United States
Completed
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Completed
Rocky Mountain Cancer CentersDenver, 80218, United States
Completed
Illinois Cancer SpecialistsArlington Heights, 60005, United States
Completed
Virginia Oncology AssociatesNewport News, 23606, United States
Completed
Texas Oncology-Arlington NorthArlington, 76012, United States
Completed
Nebraska Cancer SpecialistsPapillion, 68046, United States
Completed
Willamette Valley Cancer Institute and Research CenterEugene, 97401, United States
Completed
Miami Cancer Institute at Baptist Health South FloridaMiami, 33176, United States
Completed
Baylor Charles A. Sammons Cancer Center at DallasDallas, 75246, United States
Completed
Texas Oncology-ShermanSherman, 75090, United States
Withdrawn
Vanderbilt University Medical SchoolNashville, 37232, United States

Primary Outcome

  • 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.
    date_rangeTime Frame:
    Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)

Secondary Outcome

  • Duration of Response (DOR)
    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.
    date_rangeTime Frame:
    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
    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.
    date_rangeTime Frame:
    At 8, 16, 24, 32 and 40 weeks
  • Progression-free Survival (PFS)
    PFS was the time from first dose of study medication to disease progression or death, whichever was earlier.
    date_rangeTime Frame:
    Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
  • Overall survival (OS)
    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.
    date_rangeTime Frame:
    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
    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.
    date_rangeTime Frame:
    30 days after last dose of regorafenib and 100 days after last dose of nivolumab until study completion (up to 30 months)

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1