Dose Dense Therapy and Bevacizumab in Solid Tumors and Colorectal Cancer

The study was originally intended to be Phase I/Phase II but it was terminated early because of toxicity of treatment and therefore never moved to the Phase II portion of the study. OBJECTIVES: * Determine the maximum tolerated dose (MTD) and dose-limiting toxicity of dose-dense and dose-intense capecitabine in combination with alternating full-dose irinotecan hydrochloride and oxaliplatin in patients with metastatic or locally advanced unresectable solid tumors. (phase I) * Characterize the safety of the MTD in patients ≥ 65 years of age treated with this regimen. (phase I) * Characterize the pharmacokinetics of this regimen in patients ≥ 65 years of age. (phase I) * Characterize the functional status of patients ≥ 65 years of age at baseline and after study treatment, in terms of performance status, independence in activities, comorbidities, risk of malnutrition, and underlying depression. (phase I) * Characterize the neurological status of all patients, in terms of muscle strength and sensation, at baseline and after study treatment. (phase I) * Determine the clinical antitumor response in patients treated with this regimen. (phase I) * Determine whether the addition of bevacizumab to dose-intense capecitabine in combination with alternating full-dose irinotecan hydrochloride and oxaliplatin as first-line treatment leads to an improved response rate in patients with metastatic colorectal cancer compared to that of published results of fluoropyrimidine/oxaliplatin, fluoropyrimidine/irinotecan/bevacizumab, and fluoropyrimidine/irinotecan regimens. (phase II) * Determine the toxicity of bevacizumab in combination with this regimen in patients with metastatic colorectal cancer. (phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of capecitabine followed by a phase II study. * Phase I (all solid tumor patients): Patients receive oral capecitabine twice daily on days 1-7 and 15-21. Patients also receive irinotecan hydrochloride IV over 90 minutes on days 1 and 15 during course 1 and all subsequent odd-numbered courses and oxaliplatin IV over 2 hours on days 1 and 15 during course 2 and all subsequent even-numbered courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of capecitabine (during both odd- and even-numbered courses) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients (with at least 1 patient \< 65 years of age) experience dose-limiting toxicity. At least 6 patients are treated at the MTD. * Phase II (colorectal cancer patients): Patients receive capecitabine (at the MTD determined in phase I) in combination with irinotecan hydrochloride (during odd-numbered courses) and oxaliplatin (during even-numbered courses) as in phase I. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15 of each course. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.