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)

Conditions: Colorectal Cancer

Summary: purpose: this randomized phase iii trial is studying maintenance therapy with bevacizumab alone after an induction therapy combining bevacizumab+chemotherapy to see how well they work compared to maintenance therapy with bevacizumab+erlotinib alone after an induction therapy combining bevacizumab+chemotherapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

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.

Eligibility criteria:
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

Keywords: stage iv colon cancer stage iv rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum chemotherapy