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

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Memorial Sloan-Kettering Cancer Center
Prologue Research International
Information provided by:
US Oncology Research
ClinicalTrials.gov Identifier:
NCT00252564
First received: November 9, 2005
Last updated: February 15, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: Bevacizumab
Drug: Oxaliplatin
Drug: Leucovorin
Drug: Fluorouracil
Drug: Cetuximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by US Oncology Research:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: (no pre-determined maximum time) ] [ Designated as safety issue: No ]

    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)


  • Progression-free Survival (PFS) [ Time Frame: (no pre-determined maximum time. PFS rate at 12 months) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: (no predetermined maximum time) ] [ Designated as safety issue: No ]

    From randomization to death (event); or last follow-up date if alive (censoring).

    Kaplan-Meier OS median time.


  • Overall Response Rate [ Time Frame: (during the whole treatment period) ] [ Designated as safety issue: No ]
    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.


Enrollment: 247
Study Start Date: September 2005
Study Completion Date: June 2009
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A

(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 Name: Avastin
Drug: Oxaliplatin
85 mg/m2 on Days 1 and 15
Other Name: 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 Name: 5FU
Experimental: Arm B

(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 Name: 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 Name: 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 Name: Erbitux

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00252564

  Show 82 Study Locations
Sponsors and Collaborators
US Oncology Research
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
  More Information

No publications provided

Responsible Party: Dr. Allen Cohn, Principal Investigator, US Oncology Research
ClinicalTrials.gov Identifier: NCT00252564     History of Changes
Other Study ID Numbers: 05-041
Study First Received: November 9, 2005
Results First Received: February 15, 2011
Last Updated: February 15, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Bevacizumab
Cetuximab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 27, 2014