• Recommended phase II dose as assessed by NCI toxicity scale during 4-6 weeks of treatment [ Designated as safety issue: Yes ]
  

• Response as assessed by RECIST criteria every 8 weeks [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, the therapeutic activity of this regimen in these patients.

Secondary

• Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol when administered with this regimen in these patients.
• Determine the safety and tolerability of this regimen in these patients.
• 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 flavopiridol 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 flavopiridol 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.

PROJECTED ACCRUAL: A total of 3-46 patients will be accrued for this study within approximately 2 years.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm^3
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases)

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• 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

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 2 weeks since prior immunotherapy

Chemotherapy

• At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
• No prior flavopiridol

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior radiotherapy

Surgery

• Not specified

Other

• 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