Optimized Chemotherapy Followed by Maintenance With Bevacizumab With or Without Erlotinib in Treating Patients With Metastatic Colorectal Cancer That Cannot be Removed by Surgery (DREAM)

OBJECTIVES:

Primary

• Compare Progression-free survival during maintenance period ("Maintenance PFS")in patients with unresectable metastatic colorectal cancer.

Secondary

• Compare the duration of disease control and overall survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare the occurrence of secondary surgery in patients treated with these regimens.
• Compare the chemotherapy-free intervals and response rates in patients treated with these regimens.

INDUCTION THERAPY

Bevacizumab IV over 30-90 minutes on day 1, combined with either:

• modified FOLFOX7 (IV : oxaliplatin, folinic acid, fluorouracil),
• XELOX2 (IV : oxaliplatin, oral capecitabine day 1 to 8),
• FOLFIRI (IV : irinotecan, folinic acid, fluorouracil).

Treatment repeats every 2 weeks.

RANDOMIZATION Patients with stable or responding disease then receive maintenance therapy with bevacizumab alone or bevacizumab+erlotinib

MAINTENANCE THERAPY

• Arm A : bevacizumab alone : bevacizumab IV over 30-90 minutes on day 1
• Arm B : bevacizumab+erlotinib : bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib once daily on days 1-21.

In both arms, treatment with bevacizumab +/- erlotinib repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

ACCRUAL: A total of 700 patients will be accrued for this study.

MAIN ELIGIBILITY CRITERIA

• Histologically proven metastatic adenocarcinoma of colon or rectum
• Documented inoperable disease (i.e., not suitable for complete carcinological surgical resection)
• Measurable lesion as assessed by CT scan or MRI in at least one dimension (longest diameter to be recorded) ≥ 20 mm with conventional CT scan or ≥ 10 mm with spiral CT scan
• No previous therapy for metastatic disease
• No history or evidence upon physical examination of CNS disease (e.g., non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, or history of stroke) unless adequately treated
• No exclusive bone metastasis
• ECOG performance status 0-2
• WBC ≥ 1,500/mm^3
• Platelets ≥ 100,000/mm^3
• Hemoglobin > 9 g/dL (may be transfused to maintain or exceed this level)
• Proteinuria < 2+ by dipstick OR ≤ 1 g of protein on 24-hr urine collection
• Bilirubin < 1.5 times ULN
• Alkaline phosphatase < 3 times ULN
• No peripheral sensory neuropathy
• Negative pregnancy test
• Fertile patients must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterilization)
• No peripheral neuropathy ≥ grade 1
• No clinically significant (i.e. active) cardiovascular disease
• No evidence of bleeding diathesis or coagulopathy
• No serious, non-healing wound, ulcer, or bone fracture
• No significant ophthalmologic abnormality
• More than 28 days since prior major surgical procedure or open biopsy