OBJECTIVES: I. Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors. II. Determine the pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients. IV. Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol when administered with this regimen in these patients. V. Determine the safety and tolerability of this regimen in these patients. VI. Correlate p21, p53, and apoptotic markers with response in patients treated with this regimen. OUTLINE: This is a non-randomized, open-label, dose-escalation study of flavopiridol. Patients receive alvocidib intravenously (IV) over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of alvocidib 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 experience dose-limiting toxicity. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose.
Inclusion Criteria: * Histologically confirmed advanced solid tumor * Refractory to standard therapy or no standard therapy exists * Evaluable disease * No known untreated CNS metastases * Patients who have undergone local treatment for brain metastases and whose brain metastases are stable by repeat imaging study performed ≤ 4 weeks after treatment are allowed * No primary CNS tumors * Performance status - Karnofsky 60-100% * WBC ≥ 3,500/mm\^3 * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin ≤ 1.5 mg/dL * AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases) * Creatinine ≤ 1.5 mg/dL * No cardiac arrhythmias within the past 6 months * No congestive heart failure within the past 6 months * No myocardial infarction within the past 6 months * No arterial or venous thrombosis within the past year * No peripheral neuropathy \> grade 1 * No other medical condition that would preclude study participation * No serious or uncontrolled infection * HIV negative * Not pregnant or nursing * No nursing during and for 2 months after study participation * Negative pregnancy test * Fertile patients must use effective contraception during and for 2 months after study participation * At least 2 weeks since prior immunotherapy * At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) * No prior flavopiridol * At least 2 weeks since prior radiotherapy * Recovered from all prior therapy * No concurrent therapy for thrombosis * Prophylaxis for central lines or deep vein thrombosis allowed * No other concurrent investigational medications * No concurrent vitamins, antioxidants, or herbal preparations and supplements * Concurrent single-tablet multivitamin allowed
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