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

NCT ID: NCT00252564

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 247 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2009-06-30

Brief Summary

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.

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

5 mg/kg over 30 minutes on Days 1 and 15

Oxaliplatin

Intervention Type: DRUG

85 mg/m2 on Days 1 and 15

Leucovorin

Intervention Type: DRUG

400 mg/m2 on Days 1 and 15

Fluorouracil

Intervention Type: DRUG

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)

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

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

5 mg/kg over 30 minutes on Days 1 and 15

Leucovorin

Intervention Type: DRUG

400 mg/m2 on Days 1 and 15

Fluorouracil

Intervention Type: DRUG

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)

Cetuximab

Intervention Type: DRUG

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

Interventions

Bevacizumab

5 mg/kg over 30 minutes on Days 1 and 15

Intervention Type: DRUG

Oxaliplatin

85 mg/m2 on Days 1 and 15

Intervention Type: DRUG

Leucovorin

400 mg/m2 on Days 1 and 15

Intervention Type: 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)

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Avastin; Eloxatin; 5FU; Erbitux

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

Prologue Research International

INDUSTRY

Sponsor Role: collaborator

US Oncology Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Allen Cohn, MD

Role: PRINCIPAL_INVESTIGATOR

US Oncology Research

Leonard Saltz, M.D.

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Brimingham Hematology and Oncology

Birmingham, Alabama, United States

Hematology Oncology Associates

Phoenix, Arizona, United States

Northern AZ Hematology & Oncology Assoc

Sedona, Arizona, United States

Business Office - ACRC

Tucson, Arizona, United States

Cancer Care Associates of Fresno Medical Group, Inc (aka California Cancer Care)

Fresno, California, United States

Monterey Bay Oncology

Monterey, California, United States

Rocky Mountain Cancer Center-Midtown

Denver, Colorado, United States

Greeley Medical Clinic Oncology Hematology, PC

Greeley, Colorado, United States

Connecticut Oncology & Hematology, LLP

Torrington, Connecticut, United States

Integrated Community Oncology Network (ICON) / fka:Florida Oncology Associates

Jacksonville, Florida, United States

Melbourne Internal Medicine Associates

Melbourne, Florida, United States

Florida Cancer Institute

New Port Richey, Florida, United States

Ocala Oncology Center

Ocala, Florida, United States

Cancer Centers of Florida, P.A.

Ocoee, Florida, United States

Medical Oncology Associates of Augusta PC

Augusta, Georgia, United States

Spalding Oncology Services

Griffin, Georgia, United States

Hematology Oncology Associates of IL

Chicago, Illinois, United States

Cancer Care & Hematology Specialists of Chicagoland

Niles, Illinois, United States

Fort Wayne Medical Oncology Hematology, Inc

Fort Wayne, Indiana, United States

Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Hope Center

Terre Haute, Indiana, United States

Iowa Blood and Cancer Care

Cedar Rapids, Iowa, United States

Kansas City Cancer Centers-Southwest

Overland Park, Kansas, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Louisiana Hematology Oncology Associates

Baton Rouge, Louisiana, United States

Auerbach Hematology Oncology Associated

Baltimore, Maryland, United States

Center for Cancer & Blood Disorders

Bethesda, Maryland, United States

Maryland Oncology Hematology, P.A.

Columbia, Maryland, United States

Osteopathic Medical Oncology and Hematology

Clinton Township, Michigan, United States

Kalamazoo Hematology & Oncology

Kalamazoo, Michigan, United States

Hematology Oncology Associates of Ohio & Michigan

Lambertville, Michigan, United States

Minnesota Oncology Hematology, PA

Minneapolis, Minnesota, United States

Missouri Cancer Associates

Columbia, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Nevada Cancer Centers

Las Vegas, Nevada, United States

Hematology-Oncology Associates of NNJ, PA

Morristown, New Jersey, United States

New York Oncology Hematology, PC

Albany, New York, United States

North Shore Hematology

East Setauket, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Raleigh Hematology Oncology Associates

Cary, North Carolina, United States

Northwestern Carolina Ocology Hemato

Hickory, North Carolina, United States

Greater Dayton Cancer Center

Kettering, Ohio, United States

Willamette Valley Cancer Center

Eugene, Oregon, United States

Medical Oncology Associates

Kingston, Pennsylvania, United States

Cancer Center Associates of Carolina, PA / fka Carolina Cancer Center

Aiken, South Carolina, United States

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

C. Michael Jones, MD

Germantown, Tennessee, United States

Texas Cancer Center-Abilene (Shouth)

Abilene, Texas, United States

Texas Cancer Center

Arlington, Texas, United States

Texas Oncology Cancer Center

Austin, Texas, United States

Mamie McFaddin Ward Cancer Center

Beaumont, Texas, United States

Texas Oncology, PA - Bedford

Bedford, Texas, United States

Texas Cancer Center at Medical City

Dallas, Texas, United States

Texas Oncology, PA

Dallas, Texas, United States

The Texas Cancer Center

Dallas, Texas, United States

Texas Oncology, PA

Dallas, Texas, United States

Texas Cancer Center-Denton

Denton, Texas, United States

El Paso Cancer Treatment Ctr

El Paso, Texas, United States

Texas Oncology, PA

Fort Worth, Texas, United States

San Antonio Tumor & Blood Clinic

Fredericksburg, Texas, United States

Texas Oncology, PA

Garland, Texas, United States

Lake Vista Cancer Center

Lewisville, Texas, United States

Longview Cancer Center

Longview, Texas, United States

South Texas Cancer Center-McAllen

McAllen, Texas, United States

Texas Cancer Center of Mesquite

Mesquite, Texas, United States

Allison Cancer Center

Midland, Texas, United States

West Texas Cancer Center

Odessa, Texas, United States

Paris Regional Cancer Center

Paris, Texas, United States

HOAST - Medical Dr.

San Antonio, Texas, United States

Texas Cancer Center-Sherman

Sherman, Texas, United States

Texas Oncology Cancer Center-Sugar Land

Sugar Land, Texas, United States

Tyler Cancer Center

Tyler, Texas, United States

Waco Cancer Care and Research Center

Waco, Texas, United States

Texas Oncology, P.A.

Webster, Texas, United States

Texas Oncology, PA

Webster, Texas, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Puget Sound Cancer Center-Edmonds

Edmonds, Washington, United States

Puget Sound Cancer Center Seattle

Seattle, Washington, United States

Cancer Care Northwest-South

Spokane, Washington, United States

Northwest Cancer Specialists-Vancouver

Vancouver, Washington, United States

Yakima Valley mem Hosp/North Star Lodge

Yakima, Washington, United States

Countries

United States

Other Identifiers

05-041

Identifier Type: -

Identifier Source: org_study_id