Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: benzoylphenylurea


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: benzoylphenylurea<br> | Drug: benzoylphenylurea<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events |  | every 4 weeks | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU |  | 8 weeks | 
| Test for Antitumor Activity in Blood and Tissue |  | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific