OBJECTIVES:

• Determine the maximum tolerated dose of BMS-247550 when given in combination with carboplatin in patients with recurrent or refractory solid tumors.
• Determine the dose-limiting toxicity and safety of this regimen in these patients.
• Determine the plasma pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, any antitumor activity of this regimen in these patients.
• Correlate the protein expression of survivin with the expression of other apoptotic regulators, the apoptotic index, and response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of BMS-247550.

Patients receive BMS-247550 IV over 1 hour on days 1, 8, and 15 followed by carboplatin IV over 1 hour on day 1. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR or up to a total of 6 courses.

The first two cohorts of 3-6 patients each receive escalating doses of BMS-247550 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).

The third and fourth cohorts of 10 patients each receive escalating doses of BMS-247550 until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 10 patients experience DLT. Once the MTD is determined for the third and fourth cohorts, 15 additional patients are treated at the MTD.

Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 18-45 patients will be accrued for this study within 6-15 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
• Measurable or evaluable disease

• Lesion accessible for core or excisional biopsy if being treated at the maximum tolerated dose (MTD)

  • No biliary tract dilation if radiologically guided biopsy of the liver is planned
  • No requirement for core biopsy of lung lesion that is not pleural based
  • No requirement for laparotomy or thoracotomy solely for biopsy
  • No medical condition that would preclude biopsy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2
• ECOG 0-1 if being treated at the MTD

Life expectancy:

• More than 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No prior bleeding disorder or unexplained bleeding if being treated at the MTD

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 2 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
• PT/PTT normal

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent uncontrolled illness that would preclude study participation
• No ongoing or active infection
• No grade 2 or greater neuropathy (sensory or motor)
• No prior severe allergic reaction attributable to compounds containing Cremophor EL or platinum agents
• No psychiatric illness or social situation that would preclude study compliance
• No medical condition that would preclude study if being treated at the MTD

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 week since prior immunotherapy
• At least 24 hours since prior growth factors

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No more than 3 prior chemotherapy regimens
• No prior epothilone agents

Endocrine therapy:

• At least 1 week since prior hormonal therapy directed at malignancy
• Concurrent hormone replacement therapy allowed

Radiotherapy:

• At least 4 weeks since prior wide-field radiotherapy involving 30% or more of bone marrow

Surgery:

• See Disease Characteristics

Other:

• At least 4 weeks since prior investigational agents
• No prior or concurrent St. John's Wort
• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent heparin or other anticoagulants if being treated at the MTD
• No concurrent inhibitors of cytochrome P450 3AP (CYP3A4)