Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
NCT ID: NCT01765582
Last Updated: 2017-09-18
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
280 participants
INTERVENTIONAL
2013-01-23
2016-03-14
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: Concurrent FOLFOXIRI + Bevacizumab
Participants will receive concurrent FOLFOXIRI along with 5 mg/kg of bevacizumab with treatment cycle of 2 weeks during first 4 month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase. Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m\^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
irinotecan
Participants will receive IV infusion of 165 mg/m\^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m\^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
folinic acid
Participants will receive IV infusion of 200 mg/m\^² (Arm A) or 400 mg/m\^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m\^2 in the maintenance therapy.
oxaliplatin
Participants will receive 85 mg/m\^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
Arm B: Sequential FOLFOXIRI + Bevacizumab
Participants will receive alternating 4-week administrations of FOLFOX/bevacizumab and folinic acid (leucovorin), 5-FU, and irinotecan (FOLFIRI) /Bevacizumab with a treatment cycle of 2 weeks during first 4-month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase. Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m\^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
irinotecan
Participants will receive IV infusion of 165 mg/m\^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m\^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
folinic acid
Participants will receive IV infusion of 200 mg/m\^² (Arm A) or 400 mg/m\^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m\^2 in the maintenance therapy.
oxaliplatin
Participants will receive 85 mg/m\^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
Arm C: FOLFOX + Bevacizumab
Participants will receive FOLFOX along with 5 mg/kg of bevacizumab with treatment cycle of 2 weeks during first 4-month induction phase (plus optional 2 months of induction for participants who exhibit good response and tolerate the regimen) followed by administration of 5-FU with bevacizumab or capecitabine with bevacizumab as per investigator's discretion in maintenance phase. Following progression on first-line therapy (PD1), bevacizumab (dose equivalent, 2.5 mg/kg/week) will be administered as second-line therapy in combination with fluoropyrimidine based chemotherapy at the investigator's discretion.
5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m\^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
folinic acid
Participants will receive IV infusion of 200 mg/m\^² (Arm A) or 400 mg/m\^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m\^2 in the maintenance therapy.
oxaliplatin
Participants will receive 85 mg/m\^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
Interventions
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5-fluorouracil
Participants in Arm A will receive 3200 milligrams per square meter (mg/m\^2) by 48-hour continuous intravenous (IV) infusion every 2 weeks, during the 4-6 months' induction followed by maintenance therapy including bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks per investigator's discretion. Participants in Arm B and C will receive a bolus dose of 400 mg/m\^2, followed by a 46-hour continuous infusion (2400 mg/m\^2) every 2 weeks during the 4-6 months of induction and maintenance per investigator's discretion.
bevacizumab
Participants will receive 5 mg/kg IV every 2 weeks during the first 4-6 months induction phase, followed by 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks during maintenance therapy, and 2.5 mg/kg per week reinduction after disease progression.
capecitabine
Participants will receive 1000 or 850 mg/kg orally twice daily as per investigator's discretion on Day 1 to 14, repeated every 3 weeks in maintenance phase.
irinotecan
Participants will receive IV infusion of 165 mg/m\^2 over 1 hour every 2 weeks (Arm A) or IV infusion of 180 mg/m\^2 over 1 hour in 2 x 2 weeks cycles alternating months (in Arm B), during 4-6 months induction phase.
folinic acid
Participants will receive IV infusion of 200 mg/m\^² (Arm A) or 400 mg/m\^2 (Arm B or C) over 2 hours every 2 weeks, during 4-6 months induction phase followed by IV infusion of 400 mg/m\^2 in the maintenance therapy.
oxaliplatin
Participants will receive 85 mg/m\^2 over 2 hours as IV infusion every 2 weeks (Arm A, C ) or 2 x 2 week cycles alternating months (Arm B), during 4-6 months induction phase .
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 if age less than (\<) 71 years; ECOG status of 0 if age 71 to 75 years
* Adequate hematological, renal and liver function
* Participants with treated brain metastases are eligible for study participation; participants may not receive ongoing treatment with steroids at screening, anticonvulsants (at stable dose) are allowed
* Females of childbearing potential and males must agree to use effective contraception as defined by protocol during the treatment period and for at least 6 months after the last dose of study drug
Exclusion Criteria
* Adjuvant chemotherapy for colorectal cancer completed \< 12 months prior to study consent
* Sensory peripheral neuropathy greater than or equal to (\>/=) Grade 2
* Evidence of Gilbert's Syndrome or homozygosity for the Uridine 5-diphospho-glucuronosyltransferase (UGT) 1A1\*28 allele
* Positive for human immunodeficiency virus (HIV) infection
* Malignancies other than metastatic colorectal cancer within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
* Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
* Clinically significant third-space fluid collections (e.g. ascites or pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry
* Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization
* Any disease or condition or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of bevacizumab or puts the participant at high risk for treatment-related complications
* Inadequately controlled hypertension
* Clinically significant (that is \[i.e.\] active) cardiovascular disease (For example \[e.g.\] cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class \>/= II) or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with the administration of the study treatment
* Known hypersensitivity to bevacizumab or any of its excipients or any other study drug
18 Years
75 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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University of South Alabama; Mitchell Cancer Institute
Mobile, Alabama, United States
Long Beach Memorial Medical Center; Oncology
Long Beach, California, United States
LAC-USC Medical Center
Los Angeles, California, United States
USC Norris Cancer Center
Los Angeles, California, United States
Pacific Cancer Care - Monterey
Monterey, California, United States
Sacramento Center for Hematolo
Sacramento, California, United States
Pacific Cancer Care
Salinas, California, United States
Kaiser Permanente - Franklin
Denver, Colorado, United States
Yale Cancer Center
New Haven, Connecticut, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, United States
Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
Fort Myers, Florida, United States
Florida Cancer Specialist, North Region
St. Petersburg, Florida, United States
University Cancer & Blood Center, LLC
Athens, Georgia, United States
Emory University Clinic
Atlanta, Georgia, United States
Central Georgia Cancer Care PC
Macon, Georgia, United States
Summit Cancer Care PC
Savannah, Georgia, United States
Ingalls Memorial Hosp
Harvey, Illinois, United States
Edward Cancer Center Naperville
Naperville, Illinois, United States
Edward Cancer Center Plainfield
Plainfield, Illinois, United States
University of Kentucky Medical Center
Lexington, Kentucky, United States
Johns Hopkins Univ; Bunting Blaustein Cancer Center
Baltimore, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
St. Joseph Mercy Hospital; Cancer Care Center.
Ann Arbor, Michigan, United States
Karmanos Cancer Institute..
Detroit, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
Lincoln, Nebraska, United States
Nebraska Methodist Hospital; Cancer Center
Omaha, Nebraska, United States
Dartmouth Hitchcock Med Center
Lebanon, New Hampshire, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, United States
University of Oklahoma; Stephenson Oklahoma Canc Ctr
Oklahoma City, Oklahoma, United States
Milton S. Hershey Medical Center; Penn State Cancer Inst.
Hershey, Pennsylvania, United States
Chattanooga Oncology and Hematology Associates, PC
Chattanooga, Tennessee, United States
West Clinic
Germantown, Tennessee, United States
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, United States
UT Southwestern MC at Dallas
Dallas, Texas, United States
Ctr for Cancer and Blood Disorders
Fort Worth, Texas, United States
Scott and White Hospital; Cancer Center
Temple, Texas, United States
Virginia Cancer Institute
Richmond, Virginia, United States
Seattle Cancer Care Alliance - Evergreen Health
Kirkland, Washington, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
Medical Oncology Associates
Spokane, Washington, United States
Vince Lombardi Cancer Center
Green Bay, Wisconsin, United States
Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
Milwaukee, Wisconsin, United States
Aurora Research Institute
Wauwatosa, Wisconsin, United States
Cheyenne Oncology & Hematology Associates
Cheyenne, Wyoming, United States
Countries
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References
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Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
Hurwitz HI, Tan BR, Reeves JA, Xiong H, Somer B, Lenz HJ, Hochster HS, Scappaticci F, Palma JF, Price R, Lee JJ, Nicholas A, Sommer N, Bendell J. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14.
Other Identifiers
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ML28442
Identifier Type: -
Identifier Source: org_study_id