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)
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| ClinicalTrials.gov Identifier: NCT04126733 |
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Recruitment Status :
Completed
First Posted : October 15, 2019
Results First Posted : December 14, 2021
Last Update Posted : July 18, 2023
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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 |
| 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 |
| 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. |
- 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 (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.
- Duration of Response (DOR) [ Time Frame: 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.
- Disease Control Rate (DCR) at 8 and 16 Weeks [ Time Frame: 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.
- Progression-free Survival (PFS) [ Time Frame: 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.
- Overall Survival (OS) [ Time Frame: 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.
- 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 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.
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.
| 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
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 ClinicalTrials.gov identifier (NCT number): NCT04126733
| 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 | |
Documents provided by Bayer:
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT04126733 |
| Other Study ID Numbers: |
20975 |
| First Posted: | October 15, 2019 Key Record Dates |
| Results First Posted: | December 14, 2021 |
| Last Update Posted: | July 18, 2023 |
| Last Verified: | June 2023 |
| 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 www.clinicalstudydatarequest.com 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases |
Colonic Diseases Intestinal Diseases Rectal Diseases Nivolumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |