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

A Randomized Phase II Study of Modified FOLFOX6 (Infusional 5-Fluorouracil/Leucovorin, Oxaliplatin) and Bevacizumab With or Without Cetuximab in Patients With Metastatic Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Cetuximab; Drug: 5-fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Oncology Hematology Associates of SW Indiana
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Consultants in Blood Disorders and Cancer
  • Maine
    • Portland, Maine, United States, 04101
      • Mercy Hospital
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Louis Cancer Care
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology and Hematology Associates
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention; Bevacizumab 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

Drug: Bevacizumab; 5 mg/kg IV; Other Names: Avastin; Drug: 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; Other Names: Erbitux; Drug: 5-fluorouracil; 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient); Other Names: 5-FU; Adrucil; Drug: Leucovorin; 350 mg IV; Other Names: Folinic Acid; Drug: Oxaliplatin; 85 mg/m2 IV; Other Names: Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment	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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Disease	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.	18 months
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death	Measured from the date of first treatment until the date of death from any cause	36 months
Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab	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.	18 months

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Spigel DR, Greco FA, Waterhouse D, Shipley D, Lane CM, Vazquez ER, Clark BL, Infante JR, Bendell JC, Burris HA 3rd, Hainsworth JD. Phase II trial of FOLFOX6, bevacizumab, and cetuximab in the first-line treatment of metastatic colorectal cancer. Clin Adv Hematol Oncol. 2010 Jul;8(7):480-5, 498.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Colon Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Bevacizumab; Leucovorin; Cetuximab
• Other Study ID Numbers: SCRI GI 64