Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer (STEAM)
Colorectal Neoplasms
About this trial
This is an interventional treatment trial for Colorectal Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed colorectal cancer with at least one measurable metastatic lesion by RECIST v 1.1, that is considered unresectable at baseline
- 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:
- Any prior treatment for metastatic colorectal cancer, except for use of palliative radiosensitizers
- 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
Sites / Locations
- University of South Alabama; Mitchell Cancer Institute
- Long Beach Memorial Medical Center; Oncology
- LAC-USC Medical Center
- USC Norris Cancer Center
- Pacific Cancer Care - Monterey
- Sacramento Center for Hematolo
- Pacific Cancer Care
- Kaiser Permanente - Franklin
- Yale Cancer Center
- Sibley Memorial Hospital
- Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
- Florida Cancer Specialist, North Region
- University Cancer & Blood Center, LLC
- Emory University Clinic
- Central Georgia Cancer Care PC
- Summit Cancer Care PC
- Ingalls Memorial Hosp
- Edward Cancer Center Naperville
- Edward Cancer Center Plainfield
- University of Kentucky Medical Center
- Johns Hopkins Univ; Bunting Blaustein Cancer Center
- Tufts Medical Center
- St. Joseph Mercy Hospital; Cancer Care Center.
- Karmanos Cancer Institute..
- Washington University School of Medicine
- Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
- Nebraska Methodist Hospital; Cancer Center
- Dartmouth Hitchcock Med Center
- Oncology Hematology Care Inc
- University of Oklahoma; Stephenson Oklahoma Canc Ctr
- Milton S. Hershey Medical Center; Penn State Cancer Inst.
- Chattanooga Oncology and Hematology Associates, PC
- West Clinic
- Sarah Cannon Cancer Center and Research Institute
- UT Southwestern MC at Dallas
- Ctr for Cancer and Blood Disorders
- Scott and White Hospital; Cancer Center
- Virginia Cancer Institute
- Seattle Cancer Care Alliance - Evergreen Health
- Seattle Cancer Care Alliance
- Medical Oncology Associates
- Vince Lombardi Cancer Center
- Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
- Aurora Research Institute
- Cheyenne Oncology & Hematology Associates
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm A: Concurrent FOLFOXIRI + Bevacizumab
Arm B: Sequential FOLFOXIRI + Bevacizumab
Arm C: FOLFOX + 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.
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.
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.