RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of benzoylphenylurea in treating patients
who have advanced solid tumors.
- Determine the maximum tolerated dose of benzoylphenylurea in patients with advanced
- Evaluate the acute and chronic toxicity profile of this regimen in these patients.
- Evaluate the pharmacokinetics and metabolites of this regimen and any potential
correlation with pharmacodynamic effects in these patients.
- Determine the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral benzoylphenylurea (BPU) once weekly. Courses repeat every 4 weeks in
the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of BPU 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 a dose-limiting toxicity. Once the MTD is determined, 12 additional
patients are accrued and treated with BPU as above to confirm the MTD.
Patients are followed for 30 days.
PROJECTED ACCRUAL: Approximately 18-24 patients will be accrued for this study.
- Histologically confirmed malignancy
- Metastatic or unresectable
- No effective standard curative or palliative measures exist
- No known CNS or brain metastasis
- 18 and over
- ECOG 0-1
- Not specified
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- SGOT/SGPT normal
- Creatinine normal
- Creatinine clearance at least 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No uncontrolled ventricular arrhythmia
- No myocardial infarction within the past 3 months
- No superior vena cava syndrome
- No grade 1 or greater peripheral neuropathy
- No uncontrolled major seizure disorder
- No spinal cord compression
- No active serious infection requiring IV antibiotics
- No concurrent uncontrolled illness
- No concurrent unstable or serious medical condition
- No chronic diarrhea or malabsorption
- No history of allergic reactions to compounds similar in chemical or biological
composition to benzoylphenylurea
- No psychiatric illness or social situation that would preclude study compliance
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No concurrent immunotherapy
- No concurrent growth factors during first 2 courses of study
- Concurrent epoetin alfa allowed
- At least 28 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No other concurrent chemotherapy
- No concurrent hormonal therapy
- At least 28 days since prior large-field radiotherapy
- Prior palliative radiotherapy for painful bone metastases allowed
- No concurrent radiotherapy, including palliative or whole-brain radiotherapy for CNS
- At least 28 days since prior major surgery
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational or commercial agents or therapies for the
- No other concurrent investigational agents
- Concurrent bisphosphonates allowed if bone metastases are not only site of measurable
or evaluable disease