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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)

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Regorafenib (Stivarga, BAY73-4506)
Nivolumab (Opdivo)
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope National Medical Center
  • Rocky Mountain Cancer Centers
  • Miami Cancer Institute at Baptist Health South Florida
  • Illinois Cancer Specialists
  • Minnesota Oncology Hematology, PA
  • Nebraska Cancer Specialists
  • New York Oncology Hematology. P.C.
  • Willamette Valley Cancer Institute and Research Center
  • Sarah Cannon Cancer Center
  • Texas Oncology-Arlington North
  • Baylor Charles A. Sammons Cancer Center at Dallas
  • University of Texas MD Anderson Cancer Center
  • Texas Oncology-Sherman
  • Virginia Oncology Associates
  • Northwest Cancer Specialists, PC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Regorafenib + Nivolumab

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Progression-free Survival (PFS)
PFS was the time from first dose of study medication to disease progression or death, whichever was earlier.
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.
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.

Full Information

First Posted
October 11, 2019
Last Updated
June 25, 2023
Sponsor
Bayer
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT04126733
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 14, 2019 (Actual)
Primary Completion Date
November 11, 2020 (Actual)
Study Completion Date
March 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regorafenib + Nivolumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Regorafenib (Stivarga, BAY73-4506)
Intervention Description
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)
Intervention Type
Biological
Intervention Name(s)
Nivolumab (Opdivo)
Intervention Description
Administered on day 1 of every treatment cycle.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator
Description
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.
Time Frame
Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
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.
Time Frame
Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
Title
Disease Control Rate (DCR) at 8 and 16 Weeks
Description
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.
Time Frame
At 8, 16, 24, 32 and 40 weeks
Title
Progression-free Survival (PFS)
Description
PFS was the time from first dose of study medication to disease progression or death, whichever was earlier.
Time Frame
Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
Title
Overall Survival (OS)
Description
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.
Time Frame
Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Description
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.
Time Frame
30 days after last dose of regorafenib and 100 days after last dose of nivolumab until study completion (up to 30 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Miami Cancer Institute at Baptist Health South Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Illinois Cancer Specialists
City
Arlington Heights
State/Province
Illinois
ZIP/Postal Code
60005
Country
United States
Facility Name
Minnesota Oncology Hematology, PA
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Nebraska Cancer Specialists
City
Papillion
State/Province
Nebraska
ZIP/Postal Code
68046
Country
United States
Facility Name
New York Oncology Hematology. P.C.
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Sarah Cannon Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Texas Oncology-Arlington North
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Baylor Charles A. Sammons Cancer Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Oncology-Sherman
City
Sherman
State/Province
Texas
ZIP/Postal Code
75090
Country
United States
Facility Name
Virginia Oncology Associates
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23606
Country
United States
Facility Name
Northwest Cancer Specialists, PC
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing 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.

Learn more about this trial

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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