Clinical trial NCT00252564: Cetuximab, Bevacizumab & 5FU/Leucovorin vs. Oxaliplatin, Bevacizumab & 5FU/Leucovorin in Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
name: Memorial Sloan Kettering Cancer Center
name: Prologue Research International
First posted: 2005-11-11
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Progression-free Survival (PFS) Rate at 1 Year.
timeFrame: 12 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 4 years
measure: Objective Response Rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Brimingham Hematology and Oncology
state: Alabama
city: Phoenix
country: United States
facility: Hematology Oncology Associates
state: Arizona
city: Sedona
country: United States
facility: Northern AZ Hematology & Oncology Assoc
state: Arizona
city: Tucson
country: United States
facility: Business Office - ACRC
state: Arizona
city: Fresno
country: United States
facility: Cancer Care Associates of Fresno Medical Group, Inc (aka California Cancer Care)
state: California
city: Monterey
country: United States
facility: Monterey Bay Oncology
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Midtown
state: Colorado
city: Greeley
country: United States
facility: Greeley Medical Clinic Oncology Hematology, PC
state: Colorado
city: Torrington
country: United States
facility: Connecticut Oncology & Hematology, LLP
state: Connecticut
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network (ICON) / fka:Florida Oncology Associates
state: Florida
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Augusta
country: United States
facility: Medical Oncology Associates of Augusta PC
state: Georgia
city: Griffin
country: United States
facility: Spalding Oncology Services
state: Georgia
city: Chicago
country: United States
facility: Hematology Oncology Associates of IL
state: Illinois
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Care
state: Iowa
city: Overland Park
country: United States
facility: Kansas City Cancer Centers-Southwest
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Baton Rouge
country: United States
facility: Louisiana Hematology Oncology Associates
state: Louisiana
city: Baltimore
country: United States
facility: Auerbach Hematology Oncology Associated
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer & Blood Disorders
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Clinton Township
country: United States
facility: Osteopathic Medical Oncology and Hematology
state: Michigan
city: Kalamazoo
country: United States
facility: Kalamazoo Hematology & Oncology
state: Michigan
city: Lambertville
country: United States
facility: Hematology Oncology Associates of Ohio & Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, PA
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Centers
state: Nevada
city: Morristown
country: United States
facility: Hematology-Oncology Associates of NNJ, PA
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cary
country: United States
facility: Raleigh Hematology Oncology Associates
state: North Carolina
city: Hickory
country: United States
facility: Northwestern Carolina Ocology Hemato
state: North Carolina
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates
state: Pennsylvania
city: Aiken
country: United States
facility: Cancer Center Associates of Carolina, PA / fka Carolina Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Germantown
country: United States
facility: C. Michael Jones, MD
state: Tennessee
city: Abilene
country: United States
facility: Texas Cancer Center-Abilene (Shouth)
state: Texas
city: Arlington
country: United States
facility: Texas Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, PA - Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, PA
state: Texas
city: Dallas
country: United States
facility: The Texas Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, PA
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center-Denton
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Ctr
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, PA
state: Texas
city: Fredericksburg
country: United States
facility: San Antonio Tumor & Blood Clinic
state: Texas
city: Garland
country: United States
facility: Texas Oncology, PA
state: Texas
city: Lewisville
country: United States
facility: Lake Vista Cancer Center
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center-McAllen
state: Texas
city: Mesquite
country: United States
facility: Texas Cancer Center of Mesquite
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: Odessa
country: United States
facility: West Texas Cancer Center
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: San Antonio
country: United States
facility: HOAST - Medical Dr.
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center-Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Waco Cancer Care and Research Center
state: Texas
city: Webster
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Webster
country: United States
facility: Texas Oncology, PA
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Edmonds
country: United States
facility: Puget Sound Cancer Center-Edmonds
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center Seattle
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists-Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley mem Hosp/North Star Lodge
state: Washington
Study officials:
affiliation: US Oncology Research
name: Allen Cohn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Leonard Saltz, M.D.
role: PRINCIPAL_INVESTIGATOR
References: