Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer
Multi-Center, Randomized, Placebo-Controlled Phase II Study of Regorafenib in Combination With FOLFIRI Versus Placebo With FOLFIRI as Second-Line Therapy in Patients With Metastatic Colorectal Cancer
2 other identifiers
interventional
181
2 countries
24
Brief Summary
This randomized (2:1), multi-center, placebo-controlled, phase II efficacy study is designed to compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients with mCRC previously treated with a FOLFOX regimen.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2011
Longer than P75 for phase_2
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 16, 2011
CompletedFirst Posted
Study publicly available on registry
February 17, 2011
CompletedStudy Start
First participant enrolled
April 7, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 15, 2016
CompletedResults Posted
Study results publicly available
February 28, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 2, 2020
CompletedJanuary 6, 2021
December 1, 2020
5.6 years
February 16, 2011
November 20, 2017
December 10, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
To compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
5.5 years
Secondary Outcomes (5)
Overall Response(OR)Rate
3 years
Disease Control (DC) Rate
3 years
Overall Survival (OS)
5.5 years
Drug Metabolism
28 days
Percentage of Patients With Severe Adverse Events
3 years
Study Arms (2)
Regorafenib + FOLFIRI
ACTIVE COMPARATORregorafenib 160 mg + FOLFIRI
Placebo + FOLFIRI
PLACEBO COMPARATORPlacebo + FOLFIRI
Interventions
Regorafenib, 160 mg, PO, Days 4-10 and Days 18-24 of 28 day cycle
FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
Eligibility Criteria
You may qualify if:
- Age ≥18 years of age (no upper age limit)
- Histological or cytological documentation of adenocarcinoma of the colon or rectum
- Archived, paraffin-embedded tissue block (primary or metastatic) available for genomic studies required
- Metastatic disease not amenable to surgical resection with curative intent
- Progression during or within 6 months following administration of a standard regimen\[2\] for treatment of metastatic disease that included oxaliplatin with any of the following agents with or without bevacizumab:
- fluorouracil (F-FU) with or without leucovorin or levoleucovorin
- Capecitabine
- Note: In patients receiving FOLFOX, oxaliplatin is sometimes discontinued due to toxicity or as part of maintenance therapy strategy. If such patients progress while on 5-FU alone, they are eligible for this trial. As an example, a patient who is begun on FOLFOX or CapeOx (capecitabine with oxaliplatin, with or without bevacizumab), whose oxaliplatin is held for neurotoxicity and who is switched to capecitabine monotherapy or capecitabine with bevacizumab, would be considered to have had one prior therapy.
- Patients who develop metastatic disease within 9 months of adjuvant FOLFOX for stage II or III colon cancer
- Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (see Appendix C)
- Life expectancy of at least 3 months
- Adequate bone marrow, renal, and hepatic function, as evidenced by the following:
- absolute neutrophil count (ANC) ≥1,500/mm3
- platelets ≥100,000/mm3
- +13 more criteria
You may not qualify if:
- Prior treatment with regorafenib
- More than 1 prior chemotherapy regimen for mCRC (see section 3.1.5) Previous adjuvant FOLFOX based chemotherapy is allowed. Prior FOLFIRI or single agent irinotecan is prohibited.
- Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator
- Pregnant or breastfeeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of FOLFIRI treatment, and a negative result must be documented before start of treatment.
- History of Gilbert's syndrome
- Known Dihydropyrimidine dehydrogenase (DPD) deficiency
- Pernicious anemia or other anemias due to vitamin B12 deficiency (due to potential masking of deficiency with leucovorin)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of Day 1 of treatment with FOLFIRI
- Radiotherapy within 4 weeks prior to first dose of FOLFIRI
- Active cardiac disease including any of the following:
- Congestive heart failure (New York Heart Association (NYHA)) ≥Class 2 (see Appendix D)
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of Day 1 of FOLFIRI
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Uncontrolled hypertension. (Systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg despite optimal medical management)
- Patients with pheochromocytoma
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- UNC Lineberger Comprehensive Cancer Centerlead
- Bayercollaborator
Study Sites (24)
Rocky Mountain Cancer Centers
Denver, Colorado, 80218, United States
Mount Sinai Medical Center-Miami
Miami, Florida, 33140, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University
Atlanta, Georgia, 30322, United States
Georgia Cancer Specialists
Atlanta, Georgia, 30341, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202, United States
University of Louisville James Brown Cancer Center
Louisville, Kentucky, 40202, United States
North Shore Long Island Jewish Health System
Manhasset, New York, 11030, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Seby B. Jones Cancer Center
Boone, North Carolina, 28607, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Carolinas HealthCare System
Charlotte, North Carolina, 28262, United States
Southeast Medical Oncology Center
Goldsboro, North Carolina, 27534, United States
The Moses Cone Regional Cancer Center
Greensboro, North Carolina, 27403, United States
Leo W. Jenkins Cancer Center at ECU Medical School
Greenville, North Carolina, 27834, United States
First Health of the Carolinas, Moore Regional Hospital
Pinehurst, North Carolina, 28374, United States
Rex Cancer Center at Rex Hospital
Raleigh, North Carolina, 27607, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43221, United States
University of Virginia
Charlottesville, Virginia, 22903, United States
Portsmouth Naval Medical Center
Portsmouth, Virginia, 23708, United States
Multicare Regional Cancer Center
Tacoma, Washington, 98405, United States
Ireland Cooperative Clinical Research Group
Dublin, Ireland
Related Publications (2)
Quintanilha JCF, Geyer S, Etheridge AS, Racioppi A, Hammond K, Crona DJ, Pena CE, Jacobson SB, Marmorino F, Rossini D, Cremolini C, Sanoff HK, Abou-Alfa GK, Innocenti F. KDR genetic predictor of toxicities induced by sorafenib and regorafenib. Pharmacogenomics J. 2022 Dec;22(5-6):251-257. doi: 10.1038/s41397-022-00279-3. Epub 2022 Apr 28.
PMID: 35484400DERIVEDSchultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, Hacker UT, Kohne CH, Kornacker M, Boix O, Lettieri J, Krauss J, Fischer R, Hamann S, Strumberg D, Mross KB. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol. 2013 Jun;24(6):1560-7. doi: 10.1093/annonc/mdt056. Epub 2013 Mar 13.
PMID: 23493136DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Robin V. Johnson
- Organization
- UNC Lineberger Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Hanna Sanoff, MD
UNC Lineberger Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 16, 2011
First Posted
February 17, 2011
Study Start
April 7, 2011
Primary Completion
November 15, 2016
Study Completion
October 2, 2020
Last Updated
January 6, 2021
Results First Posted
February 28, 2018
Record last verified: 2020-12