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

Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00252564
• Other study ID #: 05-041
• Status: Completed
• Phase: Phase 3
• Start date: September 2005
• Est. completion date: June 2009

Study information

• Verified date: September 2018
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 247
• Est. completion date: June 2009
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Bevacizumab
5 mg/kg over 30 minutes on Days 1 and 15
• Oxaliplatin
85 mg/m2 on Days 1 and 15
• Leucovorin
400 mg/m2 on Days 1 and 15
• 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)
• 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

Locations

Country	Name	City	State
United States	Texas Cancer Center-Abilene (Shouth)	Abilene	Texas
United States	Cancer Center Associates of Carolina, PA / fka Carolina Cancer Center	Aiken	South Carolina
United States	New York Oncology Hematology, PC	Albany	New York
United States	Texas Cancer Center	Arlington	Texas
United States	Medical Oncology Associates of Augusta PC	Augusta	Georgia
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Auerbach Hematology Oncology Associated	Baltimore	Maryland
United States	Louisiana Hematology Oncology Associates	Baton Rouge	Louisiana
United States	Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Texas Oncology, PA - Bedford	Bedford	Texas
United States	Center for Cancer & Blood Disorders	Bethesda	Maryland
United States	Brimingham Hematology and Oncology	Birmingham	Alabama
United States	Raleigh Hematology Oncology Associates	Cary	North Carolina
United States	Iowa Blood and Cancer Care	Cedar Rapids	Iowa
United States	Hematology Oncology Associates of IL	Chicago	Illinois
United States	Osteopathic Medical Oncology and Hematology	Clinton Township	Michigan
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology, PA	Dallas	Texas
United States	Texas Oncology, PA	Dallas	Texas
United States	The Texas Cancer Center	Dallas	Texas
United States	Texas Cancer Center-Denton	Denton	Texas
United States	Rocky Mountain Cancer Center-Midtown	Denver	Colorado
United States	North Shore Hematology	East Setauket	New York
United States	Puget Sound Cancer Center-Edmonds	Edmonds	Washington
United States	El Paso Cancer Treatment Ctr	El Paso	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Fort Wayne Medical Oncology Hematology, Inc	Fort Wayne	Indiana
United States	Texas Oncology, PA	Fort Worth	Texas
United States	San Antonio Tumor & Blood Clinic	Fredericksburg	Texas
United States	Cancer Care Associates of Fresno Medical Group, Inc (aka California Cancer Care)	Fresno	California
United States	Texas Oncology, PA	Garland	Texas
United States	C. Michael Jones, MD	Germantown	Tennessee
United States	Greeley Medical Clinic Oncology Hematology, PC	Greeley	Colorado
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Spalding Oncology Services	Griffin	Georgia
United States	Northwestern Carolina Ocology Hemato	Hickory	North Carolina
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Integrated Community Oncology Network (ICON) / fka:Florida Oncology Associates	Jacksonville	Florida
United States	Kalamazoo Hematology & Oncology	Kalamazoo	Michigan
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Medical Oncology Associates	Kingston	Pennsylvania
United States	Hematology Oncology Associates of Ohio & Michigan	Lambertville	Michigan
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Nevada Cancer Centers	Las Vegas	Nevada
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	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Texas Cancer Center of Mesquite	Mesquite	Texas
United States	Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, PA	Minneapolis	Minnesota
United States	Monterey Bay Oncology	Monterey	California
United States	Hematology-Oncology Associates of NNJ, PA	Morristown	New Jersey
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	West Texas Cancer Center	Odessa	Texas
United States	Kansas City Cancer Centers-Southwest	Overland Park	Kansas
United States	Paris Regional Cancer Center	Paris	Texas
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	HOAST - Medical Dr.	San Antonio	Texas
United States	Puget Sound Cancer Center Seattle	Seattle	Washington
United States	Northern AZ Hematology & Oncology Assoc	Sedona	Arizona
United States	Texas Cancer Center-Sherman	Sherman	Texas
United States	Cancer Care Northwest-South	Spokane	Washington
United States	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas
United States	Hope Center	Terre Haute	Indiana
United States	Connecticut Oncology & Hematology, LLP	Torrington	Connecticut
United States	Business Office - ACRC	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists-Vancouver	Vancouver	Washington
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	Cancer Center of Kansas	Wichita	Kansas
United States	Yakima Valley mem Hosp/North Star Lodge	Yakima	Washington

Sponsors (4)

Lead Sponsor	Collaborator
US Oncology Research	Bristol-Myers Squibb, Memorial Sloan Kettering Cancer Center, Prologue Research International

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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