Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy
OBJECTIVES:
- Determine the maximum tolerated dose of benzoylphenylurea in patients with advanced
solid tumors.
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignancy
- Metastatic or unresectable
- No effective standard curative or palliative measures exist
- No known CNS or brain metastasis
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-1
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin normal
- SGOT/SGPT normal
Renal:
- Creatinine normal
- Creatinine clearance at least 60 mL/min
Cardiovascular:
- 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
Neurologic:
- No grade 1 or greater peripheral neuropathy
- No uncontrolled major seizure disorder
- No spinal cord compression
Other:
- 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:
Biologic therapy:
- No concurrent immunotherapy
- No concurrent growth factors during first 2 courses of study
- Concurrent epoetin alfa allowed
Chemotherapy:
- At least 28 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No other concurrent chemotherapy
Endocrine therapy:
- No concurrent hormonal therapy
Radiotherapy:
- 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
disease
Surgery:
- At least 28 days since prior major surgery
Other:
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational or commercial agents or therapies for the
malignancy
- No other concurrent investigational agents
- Concurrent bisphosphonates allowed if bone metastases are not only site of measurable
or evaluable disease
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine Maximum Tolerated Dose of BPU
Outcome Description:
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.
Outcome Time Frame:
4 weeks (1 course of treatment for each subject)
Safety Issue:
Yes
Principal Investigator
Antonio C. Wolff, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
J0072 CDR0000068625
NCT ID:
NCT00016354
Start Date:
March 2001
Completion Date:
September 2006
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
