Cetuximab, Bevacizumab & 5FU/Leucovorin vs. Oxaliplatin, Bevacizumab & 5FU/Leucovorin in Metastatic Colorectal Cancer

Randomized PhIII Trial of Cetuximab, Bevacizumab & Biweekly Infusional 5FU/Leucovorin (FOLF-CB) vs. Oxaliplatin, Bevacizumab, & Biweekly Infusional 5FU/Leucovorin (Bev-FOLFOX) in First Line Treatment of Metastatic Colorectal Cancer

The purpose of this study is to compare the rates of Progression-Free Survival (PFS) at 12 months for patients treated with Bev-FOLFOX versus patients treated with FOLF-CB for first line treatment of metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Cetuximab

Detailed Description

This is a Phase III, open label, nonblinded study. A total of 240 eligible patients will be randomized on a 1:1 basis to either treatment Arm.

In this trial, we will compare the efficacy, safety, and tolerability of this novel combination of biweekly infusional 5-FU/leucovorin plus cetuximab and bevacizumab (FOLF-CB) to the current standard of care, biweekly infusional 5-FU/leucovorin plus oxaliplatin and bevacizumab (Bev-FOLFOX). For practical purposes, this study will be a head to head comparison of oxaliplatin versus cetuximab, since the other components of both regimens will be the same.

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Brimingham Hematology and Oncology
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Hematology Oncology Associates
    • Sedona, Arizona, United States, 86336
      • Northern AZ Hematology & Oncology Assoc
    • Tucson, Arizona, United States, 85715
      • Business Office - ACRC
  • California
    • Fresno, California, United States, 93720
      • Cancer Care Associates of Fresno Medical Group, Inc (aka California Cancer Care)
    • Monterey, California, United States, 93940
      • Monterey Bay Oncology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center-Midtown
    • Greeley, Colorado, United States, 80538
      • Greeley Medical Clinic Oncology Hematology, PC
  • Connecticut
    • Torrington, Connecticut, United States, 06790
      • Connecticut Oncology & Hematology, LLP
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Integrated Community Oncology Network (ICON) / fka:Florida Oncology Associates
    • Melbourne, Florida, United States, 32901
      • Melbourne Internal Medicine Associates
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Institute
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center
    • Ocoee, Florida, United States, 34761
      • Cancer Centers of Florida, P.A.
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Medical Oncology Associates of Augusta PC
    • Griffin, Georgia, United States, 30224
      • Spalding Oncology Services
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology Oncology Associates of IL
    • Niles, Illinois, United States, 60714
      • Cancer Care & Hematology Specialists of Chicagoland
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Medical Oncology Hematology, Inc
    • Indianapolis, Indiana, United States, 46219
      • Central Indiana Cancer Centers
    • Terre Haute, Indiana, United States, 47802
      • Hope Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • Iowa Blood and Cancer Care
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer Centers-Southwest
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Louisiana Hematology Oncology Associates
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Auerbach Hematology Oncology Associated
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer & Blood Disorders
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
  • Michigan
    • Clinton Township, Michigan, United States, 48037
      • Osteopathic Medical Oncology and Hematology
    • Kalamazoo, Michigan, United States, 49048
      • Kalamazoo Hematology & Oncology
    • Lambertville, Michigan, United States, 48144
      • Hematology Oncology Associates of Ohio & Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, Pa
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89109
      • Nevada Cancer Centers
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Hematology-Oncology Associates of NNJ, PA
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, PC
    • East Setauket, New York, United States, 11733
      • North Shore Hematology
    • New York, New York, United States, 10017
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Cary, North Carolina, United States, 27511
      • Raleigh Hematology Oncology Associates
    • Hickory, North Carolina, United States, 28602
      • Northwestern Carolina Ocology Hemato
  • Ohio
    • Kettering, Ohio, United States, 45409
      • Greater Dayton Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Center
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Medical Oncology Associates
  • South Carolina
    • Aiken, South Carolina, United States, 29801
      • Cancer Center Associates of Carolina, PA / fka Carolina Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • C. Michael Jones, MD
  • Texas
    • Abilene, Texas, United States, 79606
      • Texas Cancer Center-Abilene (Shouth)
    • Arlington, Texas, United States, 76014
      • Texas Cancer Center
    • Austin, Texas, United States, 78731
      • Texas Oncology Cancer Center
    • Beaumont, Texas, United States, 77702
      • Mamie McFaddin Ward Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology, PA - Bedford
    • Dallas, Texas, United States, 75246
      • Texas Oncology, PA
    • Dallas, Texas, United States, 75230
      • Texas Cancer Center at Medical City
    • Dallas, Texas, United States, 75231
      • Texas Oncology, PA
    • Dallas, Texas, United States, 75237
      • The Texas Cancer Center
    • Denton, Texas, United States, 76210
      • Texas Cancer Center-Denton
    • El Paso, Texas, United States, 79915
      • El Paso Cancer Treatment Ctr
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, PA
    • Fredericksburg, Texas, United States, 78624
      • San Antonio Tumor & Blood Clinic
    • Garland, Texas, United States, 75042
      • Texas Oncology, PA
    • Lewisville, Texas, United States, 75067
      • Lake Vista Cancer Center
    • Longview, Texas, United States, 75601
      • Longview Cancer Center
    • McAllen, Texas, United States, 78503
      • South Texas Cancer Center-McAllen
    • Mesquite, Texas, United States, 75150
      • Texas Cancer Center of Mesquite
    • Midland, Texas, United States, 79701
      • Allison Cancer Center
    • Odessa, Texas, United States, 79761
      • West Texas Cancer Center
    • Paris, Texas, United States, 75460
      • Paris Regional Cancer Center
    • San Antonio, Texas, United States, 78229
      • HOAST - Medical Dr.
    • Sherman, Texas, United States, 75090
      • Texas Cancer Center-Sherman
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology Cancer Center-Sugar Land
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
    • Waco, Texas, United States, 76712
      • Waco Cancer Care and Research Center
    • Webster, Texas, United States, 77598
      • Texas Oncology, P.A.
    • Webster, Texas, United States, 77598
      • Texas Oncology, PA
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Edmonds, Washington, United States, 98026
      • Puget Sound Cancer Center-Edmonds
    • Seattle, Washington, United States, 98133
      • Puget Sound Cancer Center Seattle
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest-South
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists-Vancouver
    • Yakima, Washington, United States, 98902
      • Yakima Valley Mem Hosp/North Star Lodge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

• Histologically or cytologically confirmed colorectal cancer with metastatic disease
• Measurable disease
• Previously irradiated lesions will be considered evaluable, if they progressed since radiation
• Has disease other than limited to surgically resectable liver-only or lung-only metastatic disease
• Not received prior chemo and/or biotherapy for metastatic disease
• Not received oxaliplatin, bevacizumab, or cetuximab in the adjuvant setting
• May have received 5-FU, leucovorin, and/or irinotecan in the adjuvant setting, however must have remained free of disease recurrence (including free of abnormal CEA level) for 1- year or more
• Is >18 years of age
• ECOG performance status 0 or 1
• Normal organ & marrow function
• Use of an acceptable method of birth control
• Not pregnant or breast feeding
• Paraffin tissue block(s) or 12 (minimum) unstained slides available, for assessment of potential predictive markers related to the EGFR, VEGF, DNA repair, and fluoropyrimidine catabolism pathways. If no block is available, slides (typically 7 to 10 um sections, air dried on uncharged slides) may be sent
• Signed a Patient Informed Consent Form
• Signed a Patient Authorization Form (HIPAA) Form

EXCLUSION CRITERIA:

• Had prior chemotherapy for metastatic colorectal cancer
• Received any prior treatment with oxaliplatin, bevacizumab, or cetuximab in the adjuvant treatment of their colorectal cancer
• Currently receiving any other investigational anticancer agents or has participated in an experimental drug study within the past 4 weeks
• History of primary CNS tumors, seizures not well-controlled with standard medical therapy, or stroke
• Sustained hypertension, as characterized by persistent blood pressures greater than 150/100 despite medical management
• New York Heart Association (NYHA) Grade II or greater congestive heart failure or has had angioplasty or placement of coronary stents within the past 6 months
• Clinically significant peripheral vascular disease
• History of serious allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, cetuximab, oxaliplatin, fluorouracil, leucovorin, or other agents used in the study
• Received prior cetuximab or other EGFR-directed therapy, or history of prior anti-cancer murine or chimeric monoclonal antibody therapy; prior humanized and human monoclonal antibody therapy is also excluded.
• Received prior treatment with bevacizumab or other agents specifically targeting VEGF or VEGF receptors
• Uncontrolled intercurrent illness including, not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the Investigator/Treating Physician
• Serious or non-healing active wound ulcer, or active bone fracture
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of protocol treatment
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 1
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
• Current or recent use of a thrombolytic agent within last 30 days. Use for clearance of central line catheter is permitted.
• Evidence of bleeding diathesis (disorder) or clinically significant coagulopathy (Note that deep venous thrombosis is not regarded as a reason for exclusion from this trial)
• Hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• History of arterial thromboembolic events within 6 months
• Urine protein:creatinine ratio greater than 1.0 at screening
• Pregnant or lactating woman
• Known to be HIV positive or receiving combination anti-retroviral therapy
• Unable to comply with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bev-FOLFOX; (Bev-FOLFOX): Bevacizumab, followed by oxaliplatin and LV given simultaneously via "T" connector over 2 hours, followed by bolus 5-FU followed by infusional 5-FU. Bevacizumab --> oxaliplatin and LV --> bolus 5-FU --> infusional 5-FU Dosing on Days 1 and 15 of each 28-day cycle	Drug: Bevacizumab; 5 mg/kg over 30 minutes on Days 1 and 15; Other Names: Avastin; Drug: Oxaliplatin; 85 mg/m2 on Days 1 and 15; Other Names: Eloxatin; Drug: Leucovorin; 400 mg/m2 on Days 1 and 15; Drug: Fluorouracil; 400 mg/m2, IV bolus followed by: 1200 mg/m2/day via 24-hour continuous infusion, for 2 consecutive days (total 5-FU infusion dose = 2400 mg/m2 over the 48 hour period); Other Names: 5FU
Experimental: FOLF-CB; (FOLF-CB): Cetuximab administered over 2 hours (first dose only; administer all other doses over 1 hour) followed by bevacizumab over 30 minutes, followed by LV over 30 minutes, followed by bolus 5-FU followed by infusional 5-FU. Cetuximab --> bevacizumab --> LV --> bolus 5-FU --> infusional 5-FU	Drug: Bevacizumab; 5 mg/kg over 30 minutes on Days 1 and 15; Other Names: Avastin; Drug: Leucovorin; 400 mg/m2 on Days 1 and 15; Drug: Fluorouracil; 400 mg/m2, IV bolus followed by: 1200 mg/m2/day via 24-hour continuous infusion, for 2 consecutive days (total 5-FU infusion dose = 2400 mg/m2 over the 48 hour period); Other Names: 5FU; Drug: Cetuximab; 400 mg/m2 over 2 hours (Cycle 1 Day 1 only) All subsequent doses (Day 8, 15, 22 of Cycle 1 and Days 1, 8, 15, 22 other cycles)250 mg/m2 over 1 hour; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	From randomization to first progression or death, whichever comes first (event); or first new anti-cancer treatment if before or without progression / death (censoring); or last follow-up date otherwise (censoring). Kaplan-Meier median PFS time and PFS rate (at 12 months)	12 months
Progression-free Survival (PFS) Rate at 1 Year.	From randomization to first progression or death, whichever comes first (event); or first new anti-cancer treatment if before or without progression / death (censoring); or last follow-up date otherwise (censoring).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	From randomization to death (event); or last follow-up date if alive (censoring). Kaplan-Meier OS median time.	up to 4 years
Objective Response Rate	Percentage of patients with tumor response (by RECIST criteria, including complete response, or CR, i.e. disappearance of all target lesions; and partial response, or PR, i.e. at least a 30% decrease in the sum of the longest diameters of target lesions taking as reference the baseline sum of the longest diameters) among all "per-protocol population" patients.	12 months

Collaborators and Investigators

• Sponsor: US Oncology Research
• Collaborators: Bristol-Myers Squibb; Memorial Sloan Kettering Cancer Center; Prologue Research International
• Investigators: Principal Investigator: Allen Cohn, MD, US Oncology Research; Principal Investigator: Leonard Saltz, M.D., Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): June 1, 2007
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: November 9, 2005
• First Submitted That Met QC Criteria: November 10, 2005
• First Posted (Estimate): November 11, 2005

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Bevacizumab; Leucovorin; Cetuximab
• Other Study ID Numbers: 05-041