OBJECTIVES:

• Determine the dose-limiting toxicity and the maximum tolerated dose of benzoylphenylurea in patients with advanced malignancy.
• Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy

  • Metastatic or unresectable
  • No standard curative or palliative measures exist or are ineffective

• Brain metastases allowed provided 1 of the following criteria is met:

  • Lesions were previously treated with surgery, radiotherapy, or chemotherapy AND are currently asymptomatic AND no steroid therapy or antiseizure medication within the past 2 weeks
  • Untreated, asymptomatic metastases AND no requirement for steroid therapy or antiseizure medication

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 12 weeks

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

Hepatic:

• Bilirubin normal
• SGOT/SGPT no greater than 2.5 times upper limit of normal
• Albumin at least 3.0 mg/dL

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

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

Other:

• No prior allergic reactions to compounds of similar chemical or biologic composition to benzoylphenylurea
• No neuropathy greater than grade 1
• No other uncontrolled medical or psychiatric illness that would preclude study compliance
• No ongoing or active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior immunotherapy allowed
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered

Endocrine therapy:

• See Disease Characteristics
• At least 2 weeks since steroids for CNS disease

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Prior surgery allowed

Other:

• At least 2 weeks since antiseizure medications for CNS disease
• More than 7 days since prior CYP3A4 or CYP2D6 inhibitors
• More than 7 days since prior CYP3A4 inducers
• No concurrent CYP3A4 or CYP2D6 inhibitors
• No concurrent CYP3A4 inducers
• No other concurrent investigational agents
• No concurrent combination anti-retroviral therapy for HIV