Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy
- 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine Maximum Tolerated Dose of BPU
Toxicity was assessed weekly during the first 2 cycles, and monthly thereafter, using the National Cancer Institute Common Toxicity Criteria (NCI CTCv2). Dose limiting toxicity (DLT) was defined as dose delays >2 weeks, grade 4 haematologic toxicity (except grade 4 neutropenia lasting <5 days), or grade 3 nonhaematologic toxicity. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity.
4 weeks (1 course of treatment for each subject)
Antonio C. Wolff, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|