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Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00100841
Recruitment Status : Completed
First Posted : January 7, 2005
Results First Posted : July 27, 2015
Last Update Posted : July 27, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE January 6, 2005
First Posted Date  ICMJE January 7, 2005
Results First Submitted Date  ICMJE June 26, 2015
Results First Posted Date  ICMJE July 27, 2015
Last Update Posted Date July 27, 2015
Study Start Date  ICMJE November 2004
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2015)
  • Severe Adverse Event (SAE) Rate [ Time Frame: The duration of the study ]
    The primary objective is to evaluate safety in all treated patients specifically the rate of serious adverse events which were defined as grade 5 events, grade 4 hemorrhage or thrombosis or bowel perforation
  • Progression Free Survival Rate [ Time Frame: From randomization to the first documented disease progression ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer
Official Title  ICMJE Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer
Brief Summary Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab and cetuximab may kill more tumor cells. This phase II trial is studying how well giving combination chemotherapy together with bevacizumab and cetuximab works in treating patients with stage IV colorectal cancer that cannot be removed by surgery.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety, feasibility of administration, response rates and progression free survival among chemotherapy naïve patients with advanced colorectal cancer treated with FOLFOX6 plus bevacizumab and cetuximab (FBC).

II. To determine the survival of patients with advanced colorectal cancer treated with FBC.

III. To determine the safety of the current regimen in selected patients who have had prior MoAb therapy.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 60-120 minutes on day 1 in weeks 1-8. Patients also receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 48 hours on days 1 and 2 of weeks 1, 3, 5, and 7. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 40-67 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adenocarcinoma of the Rectum
  • Mucinous Adenocarcinoma of the Colon
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Signet Ring Adenocarcinoma of the Colon
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
Intervention  ICMJE
  • Biological: cetuximab
    Given IV
    Other Names:
    • C225
    • C225 monoclonal antibody
    • IMC-C225
    • MOAB C225
    • monoclonal antibody C225
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Drug: oxaliplatin
    Given IV
    Other Names:
    • 1-OHP
    • Dacotin
    • Dacplat
    • Eloxatin
    • L-OHP
  • Drug: leucovorin calcium
    Given IV
    Other Names:
    • CF
    • CFR
    • LV
  • Drug: fluorouracil
    Given IV
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
Study Arms  ICMJE Experimental: Treatment (combination chemotherapy)
Patients receive cetuximab IV over 60-120 minutes on day 1 in weeks 1-8. Patients also receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 48 hours on days 1 and 2 of weeks 1, 3, 5, and 7. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Biological: cetuximab
  • Biological: bevacizumab
  • Drug: oxaliplatin
  • Drug: leucovorin calcium
  • Drug: fluorouracil
Publications * Ocean AJ, Polite B, Christos P, Horvath L, Hamilton A, Matulich D, Chen HX, Sparano JA, Kindler HL. Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma. Clin Colorectal Cancer. 2010 Dec;9(5):290-6. doi: 10.3816/CCC.2010.n.042.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 26, 2015)
66
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum which is beyond the scope of surgical resection (MEDRA code:"Colorectal neoplasms malignant","Colorectal cancer stage IV","10010035")
  • Measurable disease,
  • Life expectancy of greater than 3 months
  • ECOG performance status =< 1
  • Leukocytes >= 3,500/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 150,000/uL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits
  • Patients may not have received prior therapy with bevacizumab or cetuximab
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to radiotherapy administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or lactating women
  • Serious or non-healing wound, ulcer or bone fracture
  • Invasive procedures defined as follows:

    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
    • Anticipation of need for major surgical procedures during the course of the study
    • Core biopsy within 7 days prior to D1 therapy
  • If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:

    • The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin
    • The subject must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)
  • Active infection requiring parental antibiotics on D1
  • Proteinuria at baseline; subjects unexpectedly discovered to have >= 1+ proteinuria will undergo a 24-hour urine collection, which will be < 1000 mg protein/ 24 hours to be allowed participation in the study
  • No currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix; patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years
  • Patients with clinically significant cardiovascular disease:

    • Uncontrolled hypertension
    • Myocardial infarction or unstable angina < 6 months prior to registration
    • New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
    • Grade II or greater peripheral vascular disease
    • CVA within 6 months of study entry
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT00100841
Other Study ID Numbers  ICMJE NCI-2012-03006
NCI-6490 ( Other Identifier: CTEP ID )
N01CM62201 ( U.S. NIH Grant/Contract )
N01CM62204 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Allyson Ocean Montefiore Medical Center
PRS Account National Cancer Institute (NCI)
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP