OBJECTIVES:

• Determine the maximum tolerated dose of BMS-214662 in patients with solid tumors.
• Evaluate intermediate biological endpoints as surrogates for the effectiveness of this drug in these patients.
• Determine the nature of dose limiting toxicity of this drug in this patient population.
• Determine the recommended phase II regimen of this drug in these patients.
• Establish a pharmacologic and pharmacokinetic profile of this drug in these patients.

OUTLINE: This is a dose escalation study.

Patients receive BMS-214662 IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months for at least 24 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of malignant solid tumor for which a standard curative therapy does not exist

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 6 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• AST no greater than 2 times upper limit of normal
• Albumin at least 3.0 g/dL

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No uncontrolled heart disease
• No history of clinically significant cardiac arrhythmia that could be exacerbated by QT interval prolongation
• Corrected QT interval no greater than 450 milliseconds

Gastrointestinal:

• Must not require total parenteral nutrition
• No manifestations of malabsorption syndrome due to prior surgery, gastrointestinal disease, or unknown reasons

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No signs or symptoms of acute infection requiring systemic therapy
• No grade 3 or 4 neurotoxicity from prior anticancer treatment or neuropathy from any cause
• No confusion, disorientation, or psychiatric illness that may preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas or mitomycin) and recovered
• No other concurrent antineoplastic agents

Endocrine therapy:

• No concurrent hormonal anticancer therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Prior drugs known to prolong the QT interval allowed if they can be safely discontinued for a time period equal to 4 elimination half-lives prior to administering study drug
• No drugs known to prolong the QT interval during and for 24 hours after study drug
• No concurrent therapy with known CYP3A4 substrates
• No other concurrent investigational agents