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OpenTrials
Completed

NCT Number: 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)

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.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

City of Hope National Medical Center, Duarte, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Regorafenib (Stivarga, BAY73-4506)

Drug

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)

Nivolumab (Opdivo)

Biological

Administered on day 1 of every treatment cycle.

Primary outcomes

  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 (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 outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  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 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.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Collaborators

  • Bristol-Myers Squibb

Registry information

Official study 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)

Important dates

Study start
2019
Primary completion
2020
Study completion
2022
First posted
Oct 15, 2019
Registry last updated
Jul 18, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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