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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00193219
First received: September 12, 2005
Last updated: March 6, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Drug: Bevacizumab
Drug: Cetuximab
Drug: 5-fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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:
  • 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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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 Death [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Measured from the date of first treatment until the date of death from any cause

  • Safety of FOLFOX6 Combined With Bevacizumab and Cetuximab [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: July 2005
Study Completion Date: July 2010
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Folinic Acid
Drug: Oxaliplatin
85 mg/m2 IV
Other Name: Eloxatin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT00193219

Locations
United States, Indiana
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Maine
Mercy Hospital
Portland, Maine, United States, 04101
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Mississippi
Jackson Oncology Associates
Jackson, Mississippi, United States, 39202
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Investigators
Principal Investigator: David R. Spigel, MD SCRI Development Innovations, LLC
  More Information

Additional Information:
Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00193219     History of Changes
Other Study ID Numbers: SCRI GI 64
Study First Received: September 12, 2005
Results First Received: December 7, 2012
Last Updated: March 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Colon Cancer

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

ClinicalTrials.gov processed this record on October 23, 2014