Regorafenib, With Cetuximab or Panitumumab, for the Treatment of Unresectable, Locally Advanced, or Metastatic Colorectal Cancer
A Randomized Phase II Study of Regorafenib Followed by Anti-EGFR Monoclonal Antibody Therapy Versus the Reverse Sequencing for Metastatic Colorectal Cancer Patients Previously Treated With Fluoropyrimidine, Oxaliplatin and Irinotecan (REVERCE II)
3 other identifiers
interventional
22
1 country
15
Brief Summary
This phase II trial how well regorafenib and anti-EGFR therapy (cetuximab or panitumumab) works for the treatment of patients with colorectal cancer that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic). Regorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab or panitumumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The purpose of this research study is to compare the effects, good and/or bad, of taking regorafenib follow by cetuximab or panitumumab, to those that receive cetuximab or panitumumab before regorafenib.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2020
Longer than P75 for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 4, 2019
CompletedFirst Posted
Study publicly available on registry
October 7, 2019
CompletedStudy Start
First participant enrolled
March 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 5, 2023
CompletedResults Posted
Study results publicly available
September 27, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2025
CompletedSeptember 27, 2024
September 1, 2024
3.5 years
October 4, 2019
June 27, 2024
September 24, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
The median OS and 95% confidence intervals in each arm will be reported.
20 months
Secondary Outcomes (6)
First Progression-free Survival (PFS)
11 months
Second PFS
3 months
Sequential Treatment PFS
12 months
Objective Response Rate
20 months
Sequential Treatment Objective Response Rate
20 months
- +1 more secondary outcomes
Study Arms (2)
Arm A (regorafenib)
EXPERIMENTALPatients receive regorafenib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If received as initial treatment, patients who experience disease progression may switch over to the other treatment regimen, per treating physician discretion.
Arm B (cetuximab, panitumumab, irinotecan)
EXPERIMENTALPatients receive cetuximab or panitumumab IV over 30-90 minutes on days 1 and 15. Patients may also receive irinotecan IV on days 1 and 15 as determined by the study doctor. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If received as initial treatment, patients who experience disease progression may switch over to the other treatment regimen, per treating physician discretion.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Histologically proven, unresectable distant metastatic or locally advanced colorectal adenocarcinoma
- KRAS, NRAS wild type
- BRAF v600E wildtype
- Measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Life expectancy of \>= 3 months per estimation of treating physician
- Absolute neutrophil count (ANC) \>= 1200/mm\^3 (obtained =\< 7 days prior to randomization)
- Platelet count \>= 75,000/mm\^3 (obtained =\< 7 days prior to randomization)
- Hemoglobin \>= 9.0 g/dL (obtained =\< 7 days prior to randomization)
- Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 7 days prior to randomization)
- Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer) (obtained =\< 7 days prior to randomization)
- Serum creatinine =\< 1.5 x ULN (obtained =\< 7 days prior to randomization)
- International normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.5 x ULN (obtained =\< 7 days prior to randomization)
- NOTE: Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
- Alkaline phosphatase limit =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement of their cancer) (obtained =\< 7 days prior to randomization)
- +8 more criteria
You may not qualify if:
- Prior treatment with regorafenib, cetuximab or panitumumab
- Major surgical procedure, open biopsy, or significant traumatic injury =\< 28 days prior to randomization
- Congestive heart failure \> New York Heart Association (NYHA) class 2.
- NOTE: Class 3 is defined as marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g., walking short distances (20-100m). They are comfortable at rest. Class 4 is defined as patients with severe limitations. Experiences symptoms even while at rest. Mostly bed bound
- Unstable angina (angina symptoms at rest), new-onset angina (begun =\< 3 months prior to randomization) or myocardial infarction =\< 6 months prior to randomization
- Cardiac arrhythmias requiring anti-arrhythmic therapy. Note: Pace makers, beta blockers or digoxin are permitted
- Uncontrolled hypertension. (Systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management)
- History of or current pheochromocytoma
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =\< 6 months prior to randomization
- Ongoing infection \> grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0
- Known history of chronic hepatitis B or C
- Patients with seizure disorder requiring medication
- Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of randomization and is clinically stable with respect to the tumor at the time of randomization. Note: Patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
- History of organ allograft (including corneal transplant)
- Evidence or history of bleeding diathesis or any hemorrhage or bleeding event \> CTCAE v5.0 grade 3 =\< 4 weeks prior to randomization
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101, United States
Cancer Center of Kansas
Wichita, Kansas, 67214, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Toledo Clinic Cancer Center
Toledo, Ohio, 43623, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Daniel H. Ahn, D.O.
- Organization
- Mayo Clinic
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel H Ahn
Academic and Community Cancer Research United
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 4, 2019
First Posted
October 7, 2019
Study Start
March 3, 2020
Primary Completion
September 5, 2023
Study Completion
March 31, 2025
Last Updated
September 27, 2024
Results First Posted
September 27, 2024
Record last verified: 2024-09