Clinical trial NCT01765582: Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
Official title: Steam (Sequencing Triplet With Avastin and Maintenance): FOLFOXIRI/Bevacizumab Regimens (Concurrent and Sequential) vs. FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-01-10
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Percentage of Participants With Overall Response During First-Line Therapy (ORR1)
timeFrame: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
measure: Progression-Free Survival During First-Line Therapy (PFS1)
timeFrame: Randomization up to disease progression during first-line therapy or death, whichever occurs first (up to approximately 3 years)
Secondary outcomes:
measure: Time to PFS2
timeFrame: Randomization up to disease progression during second-line therapy or death, whichever occurs first (up to approximately 3 years)
measure: Overall Survival (OS)
timeFrame: Randomization until death due to any cause (up to approximately 3 years)
measure: Proportion of Participants Who Underwent Liver Metastases Resections
timeFrame: Randomization up to approximately 3 years
measure: Proportion of Participants Considered by the Investigator to be Unresectable on Study Enrollment Who Subsequently Underwent Attempted Curative Resections of Metastases
timeFrame: Randomization up to approximately 3 years
measure: Percentage of Participants With Adverse Events
timeFrame: Randomization up to approximately 3 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama; Mitchell Cancer Institute
state: Alabama
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center; Oncology
state: California
city: Los Angeles
country: United States
facility: LAC-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Monterey
country: United States
facility: Pacific Cancer Care - Monterey
state: California
city: Sacramento
country: United States
facility: Sacramento Center for Hematolo
state: California
city: Salinas
country: United States
facility: Pacific Cancer Care
state: California
city: Denver
country: United States
facility: Kaiser Permanente - Franklin
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington, D.C.
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist, North Region
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Atlanta
country: United States
facility: Emory University Clinic
state: Georgia
city: Macon
country: United States
facility: Central Georgia Cancer Care PC
state: Georgia
city: Savannah
country: United States
facility: Summit Cancer Care PC
state: Georgia
city: Harvey
country: United States
facility: Ingalls Memorial Hosp
state: Illinois
city: Naperville
country: United States
facility: Edward Cancer Center Naperville
state: Illinois
city: Plainfield
country: United States
facility: Edward Cancer Center Plainfield
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Univ; Bunting Blaustein Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital; Cancer Care Center.
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute..
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Methodist Hospital; Cancer Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Med Center
state: New Hampshire
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma; Stephenson Oklahoma Canc Ctr
state: Oklahoma
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center; Penn State Cancer Inst.
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Associates, PC
state: Tennessee
city: Germantown
country: United States
facility: West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center and Research Institute
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern MC at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Ctr for Cancer and Blood Disorders
state: Texas
city: Temple
country: United States
facility: Scott and White Hospital; Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Kirkland
country: United States
facility: Seattle Cancer Care Alliance - Evergreen Health
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Green Bay
country: United States
facility: Vince Lombardi Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
state: Wisconsin
city: Wauwatosa
country: United States
facility: Aurora Research Institute
state: Wisconsin
city: Cheyenne
country: United States
facility: Cheyenne Oncology & Hematology Associates
state: Wyoming
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.