Erlotinib, Modified FOLFOX6, and Bevacizumab as First-Line Therapy Metastatic Colorectal Cancer

OBJECTIVES:

• Determine the toxicity of erlotinib, mFOLFOX6, and bevacizumab in patients with metastatic colorectal cancer.
• Determine the efficacy of this regimen in these patients.
• Determine the feasibility of escalating the dose of erlotinib in order to maximize the likelihood of developing a grade 2 skin rash in select patients.

OUTLINE: This is a multicenter study.

• Single-agent erlotinib: Patients receive oral erlotinib once daily on days 1-14 (course 1).
• Erlotinib, modified FOLFOX6, and bevacizumab chemotherapy: Patients receive oral erlotinib* once daily on days 1-14, oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2 in course 2. Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

NOTE: Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Biopsy-accessible metastatic disease
• Measurable disease
• No CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• WBC ≥ 4,000/mm^3 OR
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• No bleeding disorder

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• Albumin ≥ 2.5 g/dL

Renal

• Creatinine ≤ 1.5 mg/dL
• Urine protein:creatine ratio < 1.0

Cardiovascular

• Blood pressure ≤ 150/100 mmHg
• No arterial thrombotic event within the past 6 months
• No New York Heart Association grade II-IV congestive heart failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after completion of study treatment
• No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other malignancy with < 10% chance of relapse within 3 years
• No uncontrolled infection
• No severe uncontrolled illness that would preclude study participation
• No peripheral neuropathy interfering with function
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No serious non-healing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent sargramostim (GM-CSF)

Chemotherapy

• No prior chemotherapy, including oxaliplatin, for metastatic disease
• Prior adjuvant oxaliplatin allowed provided disease progressed > 12 months after completion of oxaliplatin
• At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas)

• No more than 2 courses of prior mitomycin
• No concurrent chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• At least 2 weeks since prior radiotherapy
• No prior radiotherapy to > 15% of bone marrow
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgery
• At least 1 week since prior minor surgery

Other

• Recovered from prior therapy
• No prior epidermal growth factor receptor inhibitor therapy
• No other concurrent antineoplastic or antitumor therapy
• No other concurrent investigational agents