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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04126733
Recruitment Status : Completed
First Posted : October 15, 2019
Results First Posted : December 14, 2021
Last Update Posted : May 9, 2022
Bristol-Myers Squibb
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Regorafenib (Stivarga, BAY73-4506) Biological: Nivolumab (Opdivo) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 14, 2019
Actual Primary Completion Date : November 11, 2020
Actual Study Completion Date : March 28, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Regorafenib + Nivolumab Drug: Regorafenib (Stivarga, BAY73-4506)
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)

Biological: Nivolumab (Opdivo)
Administered on day 1 of every treatment cycle.

Primary Outcome Measures :
  1. Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator [ Time Frame: Through Database Cut-off Date of 11-NOV-2020 (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 :
  1. Duration of Response (DOR) [ Time Frame: Through Database Cut-off Date of 11-NOV-2020 (up to 13 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.

  2. Disease Control Rate (DCR) at 8 and 16 Weeks [ Time Frame: 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.

  3. Progression-free Survival (PFS) [ Time Frame: Through Database Cut-off Date of 11-NOV-2020 (up to 13 months) ]
    PFS was the time from first dose of study medication to disease progression or death, whichever was earlier.

  4. Overall Survival (OS) [ Time Frame: Through Database Cut-off Date (DCO) of 11-NOV-2020 (up to 13 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.

  5. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5 [ Time Frame: 30 Days after Last Dose of Regorafenib and 100 Days after Last Dose of Nivolumab until Data Cut-off Date of 11-NOV-2020 (up to 13 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.) until the data cut-off date for this analysis.

    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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04126733

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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Florida
Miami Cancer Institute at Baptist Health South Florida
Miami, Florida, United States, 33176
United States, Illinois
Illinois Cancer Specialists
Arlington Heights, Illinois, United States, 60005
United States, Minnesota
Minnesota Oncology Hematology, PA
Minneapolis, Minnesota, United States, 55404
United States, Nebraska
Nebraska Cancer Specialists
Papillion, Nebraska, United States, 68046
United States, New York
New York Oncology Hematology. P.C.
Albany, New York, United States, 12206
United States, Oregon
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, United States, 97401
United States, Tennessee
Sarah Cannon Cancer Center
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology-Arlington North
Arlington, Texas, United States, 76012
Baylor Charles A. Sammons Cancer Center at Dallas
Dallas, Texas, United States, 75246
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Oncology-Sherman
Sherman, Texas, United States, 75090
United States, Virginia
Virginia Oncology Associates
Newport News, Virginia, United States, 23606
United States, Washington
Northwest Cancer Specialists, PC
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bayer:
Study Protocol  [PDF] November 18, 2020
Statistical Analysis Plan  [PDF] November 11, 2020

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Responsible Party: Bayer Identifier: NCT04126733    
Other Study ID Numbers: 20975
First Posted: October 15, 2019    Key Record Dates
Results First Posted: December 14, 2021
Last Update Posted: May 9, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action