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A Study of Sequential and Concurrent FOLFOXIRI/Avastin (Bevacizumab) Regimens Versus FOLFOX/Avastin in First-Line in Participants With Metastatic Colorectal Cancer (STEAM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01765582
First received: January 9, 2013
Last updated: March 7, 2017
Last verified: January 2017
  Purpose
This randomized, open-label, multicenter study will evaluate the efficacy and safety of folinic acid (leucovorin), 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) / bevacizumab regimens (concurrent and sequential) versus folinic acid (leucovorin), 5-fluorouracil, and oxaliplatin (FOLFOX) / bevacizumab in first-line in participants with metastatic colorectal cancer. Participants will be randomized to receive bevacizumab 5 milligrams per kilogram (mg/kg) intravenously every 2 weeks with either concurrent or sequential FOLFOXIRI or with FOLFOX for 4 to 6 months of induction therapy, followed by maintenance therapy with bevacizumab plus either leucovorin/5-fluorouracil or capecitabine until disease progression occurs. After disease progression, participants will receive treatment with a fluoropyrimidine-based chemotherapy plus bevacizumab.

Condition Intervention Phase
Colorectal Neoplasm
Drug: 5-fluorouracil
Drug: bevacizumab
Drug: Capecitabine
Drug: Irinotecan
Drug: Leucovorin
Drug: Oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Steam (Sequencing Triplet With Avastin and Maintenance): FOLFOXIRI/Bevacizumab Regimens (Concurrent and Sequential) vs. FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Overall Response During First-Line Therapy (ORR1), Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) [ Time Frame: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years) ]
  • Progression-Free Survival During First-Line Therapy (PFS1), Assessed by Investigator According to RECIST v.1.1 Criteria [ Time Frame: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years) ]

Secondary Outcome Measures:
  • Percentage of Participants With Overall Response During Second-Line Therapy (ORR2), Assessed by Investigator According to RECIST v.1.1 [ Time Frame: After initiation of second-line therapy up to disease progression or death, whichever occurs first (up to approximately 3 years) ]
  • Progression-Free Survival During Second-Line Therapy (PFS2) Assessed by Investigator According to RECIST v.1.1 Criteria [ Time Frame: After initiation of second-line therapy up to disease progression or death, whichever occurs first (up to approximately 3 years) ]
  • Time to PFS2, Assessed by Investigator According to RECIST v.1.1 Criteria [ Time Frame: Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years) ]
  • Overall survival (OS) [ Time Frame: Randomization until death due to any cause (up to approximately 3 years) ]
  • Percentage of Participants who Underwent Liver Metastases Resections [ Time Frame: Randomization up to approximately 3 years ]
  • Percentage of Participants Considered by the Investigator to be Unresectable on Study Enrollment Who Subsequently Undergo Attempted Curative Resections of Metastases [ Time Frame: Randomization up to approximately 3 years ]
  • Percentage of Participants With Adverse Events [ Time Frame: Randomization up to approximately 3 years ]

Enrollment: 48
Study Start Date: January 2013
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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. Participant 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.
Drug: 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.
Other Name: Avastin
Drug: 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.
Other Name: Xeloda
Drug: 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.
Drug: Leucovorin
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.
Drug: 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 .
Experimental: 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.
Drug: 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. Participant 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.
Drug: 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.
Other Name: Avastin
Drug: 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.
Other Name: Xeloda
Drug: 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.
Drug: Leucovorin
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.
Drug: 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 .
Experimental: 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.
Drug: 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. Participant 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.
Drug: 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.
Other Name: Avastin
Drug: 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.
Other Name: Xeloda
Drug: Leucovorin
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.
Drug: 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 .

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765582

  Hide Study Locations
Locations
United States, Alabama
University of South Alabama; Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, California
Long Beach Memorial Medical Center; Oncology
Long Beach, California, United States, 90806
LAC-USC Medical Center
Los Angeles, California, United States, 90033
USC Norris Cancer Center
Los Angeles, California, United States, 90033
Pacific Cancer Care - Monterey
Monterey, California, United States, 93940
Sacramento Center for Hematolo
Sacramento, California, United States, 95816
Pacific Cancer Care
Salinas, California, United States, 93901
United States, Colorado
Kaiser Permanente - Franklin
Denver, Colorado, United States, 80205
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Florida
Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
Fort Myers, Florida, United States, 33905
Florida Cancer Specialist, North Region
St Petersburg, Florida, United States, 33705
United States, Georgia
University Cancer & Blood Center, LLC
Athens, Georgia, United States, 30607
Emory University Clinic
Atlanta, Georgia, United States, 30322
Central Georgia Cancer Care PC
Macon, Georgia, United States, 31201
Summit Cancer Care PC
Savannah, Georgia, United States, 31405
United States, Illinois
Ingalls Memorial Hosp
Harvey, Illinois, United States, 60426
Edward Cancer Center Naperville
Naperville, Illinois, United States, 60540
Edward Cancer Center Plainfield
Plainfield, Illinois, United States, 60585
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536
United States, Maryland
Johns Hopkins Univ; Bunting Blaustein Cancer Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
St. Joseph Mercy Hospital; Cancer Care Center.
Ann Arbor, Michigan, United States, 48106
Karmanos Cancer Institute..
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
Lincoln, Nebraska, United States, 68510
Nebraska Methodist Hospital; Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Hampshire
Dartmouth Hitchcock Med Center
Lebanon, New Hampshire, United States, 03756
United States, Ohio
Oncology Hematology Care Inc
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
University of Oklahoma; Stephenson Oklahoma Canc Ctr
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Milton S. Hershey Medical Center; Penn State Cancer Inst.
Hershey, Pennsylvania, United States, 17033
United States, Tennessee
Chattanooga Oncology and Hematology Associates, PC
Chattanooga, Tennessee, United States, 37404
West Clinic
Germantown, Tennessee, United States, 38138
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
UT Southwestern MC at Dallas
Dallas, Texas, United States, 75390-9063
Ctr for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
Scott and White Hospital; Cancer Center
Temple, Texas, United States, 76508
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23226
United States, Washington
Seattle Cancer Care Alliance - Evergreen Health
Kirkland, Washington, United States, 98034
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Medical Oncology Associates
Spokane, Washington, United States, 99208
United States, Wisconsin
Vince Lombardi Cancer Center
Green Bay, Wisconsin, United States, 54311
Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
Milwaukee, Wisconsin, United States, 53226
Aurora Research Institute
Wauwatosa, Wisconsin, United States, 53226
United States, Wyoming
Cheyenne Oncology & Hematology Associates
Cheyenne, Wyoming, United States, 82001
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01765582     History of Changes
Other Study ID Numbers: ML28442
Study First Received: January 9, 2013
Last Updated: March 7, 2017

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Irinotecan
Bevacizumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on March 27, 2017