MedPath

Bevacizumab and Cetuximab in Combination With FOLFOX6 in Patients With Metastatic Colorectal Cancer

Registration Number
NCT00193219
Lead Sponsor
SCRI Development Innovations, LLC
Brief Summary

This trial will evaluate the combination of modified infusional 5-fluorouracil/ leucovorin, oxaliplatin (FOLFOX6), bevacizumab, and cetuximab in patients with metastatic colorectal cancer. FOLFOX6 has proven to be a safe and effective regimen in first line treatment of advanced colorectal cancer. The role of epidermal growth factor (EGFR) inhibitors in an earlier treatment setting in combination with optimal chemotherapy regimens is an important emerging question.

Detailed Description

All patients received cetuximab: 400 mg/m2 (first cycle only) administered intravenously (IV) on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8. Day 1 cetuximab was immediately followed by bevacizumab 5 mg/kg IV, oxaliplatin 85 mg/m2 IV, and 5-fluorouracil 400 mg/m2 IV bolus, followed by 2400 mg/m2 administered as a continuous infusion over 46 hours via a pump (outpatient) and leucovorin 350 mg IV (modified FOLFOX6). Cycles were 14 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
Inclusion Criteria

To be included in the study, you must meet the following criteria:

  • Metastatic colorectal cancer confirmed by a biopsy sample
  • 18 years of age or older
  • Evidence of disease progression at time of study entry
  • At least one prior adjuvant chemotherapy regimen
  • No prior therapy for metastatic disease
  • Measurable disease
  • Able to perform activities of daily living with minimal assistance
  • Adequate bone marrow, kidney, and liver function
  • Tumor tissue available for assessment of EGFR
  • Signed informed consent
Exclusion Criteria

You cannot participate in the study if any of the following apply to you:

  • Treatment with a previous regimen for metastatic disease
  • Prior treatment with any EGFR inhibitor or anti-angiogenic agents
  • Brain or nervous system metastases
  • History of severe thromboembolic event
  • Clinical evidence or history of bleeding or coagulopathy
  • History of stroke or heart attack within six months
  • Poorly controlled hypertension
  • Non-healing wound, ulcer, or bone fracture
  • History of abdominal fistula, perforation, or abscess within six months
  • Other uncontrolled or significant disease or medical condition

Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
InterventionCetuximabBevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
InterventionBevacizumabBevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
InterventionOxaliplatinBevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
Intervention5-fluorouracilBevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
InterventionLeucovorinBevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
Primary Outcome Measures
NameTimeMethod
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment18 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease18 months

Progression Free Survival (PFS) is defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death.

Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death36 months

Measured from the date of first treatment until the date of death from any cause

Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab18 months

The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here.

Trial Locations

Locations (10)

St. Louis Cancer Care

🇺🇸

Chesterfield, Missouri, United States

Jackson Oncology Associates

🇺🇸

Jackson, Mississippi, United States

Chattanooga Oncology and Hematology Associates

🇺🇸

Chattanooga, Tennessee, United States

Mercy Hospital

🇺🇸

Portland, Maine, United States

Oncology Hematology Associates of SW Indiana

🇺🇸

Evansville, Indiana, United States

Consultants in Blood Disorders and Cancer

🇺🇸

Louisville, Kentucky, United States

Methodist Cancer Center

🇺🇸

Omaha, Nebraska, United States

Oncology Hematology Care

🇺🇸

Cincinnati, Ohio, United States

Tennessee Oncology

🇺🇸

Nashville, Tennessee, United States

Center for Cancer and Blood Disorders

🇺🇸

Bethesda, Maryland, United States

© Copyright 2025. All Rights Reserved by MedPath