RATIONALE: 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.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the colon adenocarcinoma of the rectum stage IV colon cancer Stage IV rectal cancer recurrent colon cancer recurrent rectal cancer	Drug: bevacizumab  Drug: cetuximab  Drug: fluorouracil  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the safety and feasibility of oxaliplatin, fluorouracil, leucovorin calcium, bevacizumab, and cetuximab in patients with unresectable stage IV colorectal cancer.
• Determine the response rate and progression-free survival of patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.
• Determine the safety of this regimen in patients who have received prior monoclonal antibody therapy.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 30-120 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Unresectable stage IV disease
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,500/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 150,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine normal
• No proteinuria OR
• Less than 1,000 mg protein on 24-hour urine collection

Cardiovascular

• No uncontrolled hypertension
• No New York Heart Association class II-IV congestive heart failure
• No unstable angina pectoris within the past 6 months
• No peripheral vascular disease ≥ grade 2
• No serious cardiac arrhythmia requiring medication
• No myocardial infarction within the past 6 months
• No cerebrovascular accident within the past 6 months
• No other clinically significant cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No history of allergic reaction to compounds of similar chemical or biologic composition to study drugs
• No other uncontrolled illness that would preclude study participation
• No ongoing or active infection requiring parenteral antibiotics
• No serious or non-healing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 28 days
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior bevacizumab or cetuximab

Chemotherapy

• No more than 1 prior chemotherapy regimen
• No prior oxaliplatin

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered

Surgery

• More than 28 days since prior major surgery or open biopsy
• More than 7 days since prior core biopsy
• No concurrent major surgery

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies for the malignancy
• No other concurrent anticancer therapy
• Concurrent full-dose anticoagulants allowed provided the following criteria are met:
• INR in normal range on a stable dose of warfarin or low molecular weight heparin
• No active bleeding
• No pathological condition that would confer a high risk of bleeding (e.g., tumor with major blood vessel involvement or known varices)

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10467,  United States; Recruiting
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Australia, New South Wales
      Sydney Cancer Centre at Royal Prince Alfred Hospital, Sydney,  New South Wales,  2050,  Australia; Recruiting

Study chairs or principal investigators

Scott Wadler, MD,  Principal Investigator,  Cornell University Medical College   

Study ID Numbers:  CDR0000409570; NYWCCC-1004-528; NCI-6490; NCT00100841
Record last reviewed:  January 2005
Last Updated:  April 4, 2005
Record first received:  January 6, 2005
ClinicalTrials.gov Identifier:  NCT00100841
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08