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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01765582
First received: January 9, 2013
Last updated: March 2, 2015
Last verified: March 2015
  Purpose

This randomized, open-label, multicenter study will evaluate the efficacy and safety of FOLFOXIRI/Avastin (bevacizumab) regimens (concurrent and sequential) versus FOLFOX/Avastin in first-line in patients with metastatic colorectal cancer. Patients will be randomized to receive Avastin 5 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 Avastin plus either leucovorin/5-fluorouracil or capecitabine until disease progression occurs. After disease progression, patients will receive treatment with a fluoropyrimidine-based chemotherapy plus Avastin.


Condition Intervention Phase
Colorectal Cancer
Drug: 5-fluorouracil
Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Drug: fluoropyrimidine-based chemotherapy
Drug: irinotecan
Drug: leucovorin
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: STEAM (SEQUENTIAL TRIPLET AND AVASTIN 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:
  • Overall response rate (ORR1) during first-line therapy, assessed by the investigator according to RECIST v.1.1 criteria [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS1), defined as time from randomization to first occurrence of disease progression or death, whichever occurs first, during first-line therapy [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate during second-line therapy (ORR2), defined as proportion of patients with complete response or partial response during second-line therapy [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Progression-free survival during second-line therapy (PFS2), defined as time from reinduction of second-line therapy to disease progression or death from any cause, whichever occurs first [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Time to PFS2, defined as time from randomization to first occurrence of disease progression after reintroduction of second-line therapy [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Overall survival, defined as time from randomization to death of any cause [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Liver resection rate: Proportion of patients who undergo liver metastases resections [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Rates of conversion from unresectable to resectable disease (liver-limited and non-liver-limited disease) [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]

Enrollment: 280
Study Start Date: January 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: FOLFOXIRI + bevacizumab Drug: 5-fluorouracil
iv every 2 weeks, 4-6 months induction followed by maintenance therapy
Drug: bevacizumab [Avastin]
5 mg/kg iv every 2 weeks, 4-6 months induction, followed by 5 mg/kg iv every 2 weeks or 7.5 mg/kg iv every 3 weeks maintenance therapy, and 2.5 mg/kg/week reinduction after disease progression
Drug: capecitabine [Xeloda]
1000 or 850 mg/kg orally b.i.d. Day 1-14, repeated every 3 weeks, maintenance phase
Drug: fluoropyrimidine-based chemotherapy
reinduction therapy after disease progression
Drug: irinotecan
iv every 2 weeks (Arm A) or iv 2 x 2 weeks cycles alternating months (Arm B), 4-6 months induction
Drug: leucovorin
iv every 2 weeks, 4-6 months induction followed by maintenance therapy
Experimental: B: sequential FOLFOXIRI + bevacizumab Drug: 5-fluorouracil
iv every 2 weeks, 4-6 months induction followed by maintenance therapy
Drug: bevacizumab [Avastin]
5 mg/kg iv every 2 weeks, 4-6 months induction, followed by 5 mg/kg iv every 2 weeks or 7.5 mg/kg iv every 3 weeks maintenance therapy, and 2.5 mg/kg/week reinduction after disease progression
Drug: capecitabine [Xeloda]
1000 or 850 mg/kg orally b.i.d. Day 1-14, repeated every 3 weeks, maintenance phase
Drug: fluoropyrimidine-based chemotherapy
reinduction therapy after disease progression
Drug: irinotecan
iv every 2 weeks (Arm A) or iv 2 x 2 weeks cycles alternating months (Arm B), 4-6 months induction
Drug: leucovorin
iv every 2 weeks, 4-6 months induction followed by maintenance therapy
Drug: oxaliplatin
iv every 2 weeks (Arm C) or 2 x 2 week cycles alternating months (Arm B), 4-6 months induction
Experimental: C: FOLFOX + bevacizumab Drug: 5-fluorouracil
iv every 2 weeks, 4-6 months induction followed by maintenance therapy
Drug: bevacizumab [Avastin]
5 mg/kg iv every 2 weeks, 4-6 months induction, followed by 5 mg/kg iv every 2 weeks or 7.5 mg/kg iv every 3 weeks maintenance therapy, and 2.5 mg/kg/week reinduction after disease progression
Drug: capecitabine [Xeloda]
1000 or 850 mg/kg orally b.i.d. Day 1-14, repeated every 3 weeks, maintenance phase
Drug: fluoropyrimidine-based chemotherapy
reinduction therapy after disease progression
Drug: leucovorin
iv every 2 weeks, 4-6 months induction followed by maintenance therapy
Drug: oxaliplatin
iv every 2 weeks (Arm C) or 2 x 2 week cycles alternating months (Arm B), 4-6 months induction

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 and </= 75 years of age
  • Histologically confirmed colorectal cancer with at least one measurable metastatic lesion by RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate hematological, renal and liver function
  • Patients with treated brain metastases are eligible for study participation; patients 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 >/= grade 2
  • Evidence of Gilbert's Syndrome or homozygosity for the UGT1A1*28 allele
  • Positive for 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 an other investigational drug trial within 28 days prior to randomization
  • Pregnant or breastfeeding women
  • Any disease or condition or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of bevacizumab or puts the patient at high risk for treatment-related complications
  • Inadequately controlled hypertension
  • Clinically significant (i.e. active) cardiovascular disease (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
Mobile, Alabama, United States, 36604
United States, California
Long Beach, California, United States, 90806
Los Angeles, California, United States, 90033
Monterey, California, United States, 93940
Sacramento, California, United States, 95816
Salinas, California, United States, 93901
United States, Colorado
Denver, Colorado, United States, 80205
United States, Connecticut
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Washington, District of Columbia, United States, 20016
United States, Florida
Fort Myers, Florida, United States, 33905
St Petersburg, Florida, United States, 33705
United States, Georgia
Athens, Georgia, United States, 30607
Atlanta, Georgia, United States, 30322
Macon, Georgia, United States, 31201
Savannah, Georgia, United States, 31405
United States, Illinois
Harvey, Illinois, United States, 60426
Naperville, Illinois, United States, 60540
Plainfield, Illinois, United States, 60585
United States, Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Boston, Massachusetts, United States, 02111
United States, Michigan
Ann Arbor, Michigan, United States, 48106
Detroit, Michigan, United States, 48201
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Nebraska
Lincoln, Nebraska, United States, 68510
Omaha, Nebraska, United States, 68114
United States, New Hampshire
Lebanon, New Hampshire, United States, 03756
United States, Ohio
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Hershey, Pennsylvania, United States, 17033
United States, Tennessee
Chattanooga, Tennessee, United States, 37404
Memphis, Tennessee, United States, 38120
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75390-9063
Fort Worth, Texas, United States, 76104
Temple, Texas, United States, 76508
United States, Virginia
Richmond, Virginia, United States, 23230
United States, Washington
Kirkland, Washington, United States, 98034
Seattle, Washington, United States, 98109
Spokane, Washington, United States, 99208
United States, Wisconsin
Green Bay, Wisconsin, United States, 54311
Milwaukee, Wisconsin, United States, 53226
Wauwatosa, Wisconsin, United States, 53226
United States, Wyoming
Cheyenne, Wyoming, United States, 82001
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

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 2, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 30, 2015