Benzoylphenylurea in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of benzoylphenylurea in treating patients with advanced cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

Detailed Description
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OBJECTIVES: I. Determine the dose-limiting toxicity and the maximum tolerated dose of benzoylphenylurea in patients with advanced malignancy. II. 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.

Official Title
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Phase I Trial Of Benzoylphenylurea (NSC#639829) In Advanced Malignancy

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: benzoylphenylurea
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Performance status - ECOG 0-2 More than 12 weeks WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal SGOT/SGPT no greater than 2.5 times upper limit of normal Albumin at least 3.0 mg/dL Creatinine normal Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia 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 immunotherapy allowed No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered At least 2 weeks since steroids for CNS disease At least 4 weeks since prior radiotherapy and recovered Prior surgery allowed 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

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: Treatment (benzoylphenylurea)<br>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. | Drug: benzoylphenylurea<br>* Given orally<br>* Other names: BPU;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum-tolerated dose (MTD) defined as the highest dose level where 0/6 or 1/6 patients experience dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0 |  | 8 weeks | 
| DLT defined as grade 3 or worse non-hematologic and sustained (> 5 days) grade 3 hematologic toxicity or grade 4 hematologic toxicity of any duration, and the moderate toxicity is grade 2 toxicity as assessed by CTCAE version 3.0 |  | 8 weeks | 
| Pharmacokinetics of benzoylphenylurea | Relationships between drug exposure and toxicity, efficacy, and biological endpoints will be explored using univariate and multivariate analysis techniques. | At baseline, at 0.5, 1.0, 1.5, 2, 4, 6, 8, 24, 48, 72, and 96 hours (weeks 1 and 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response (complete and partial response) rate | Response rate will be evaluated for all patients with measurable disease and will be obtained by dividing the total number of responses by all patients with measurable disease and reported with 95% confidence intervals. | Up to 7 years | 
| Survival | The median and landmark survivals will be estimated utilizing the Kaplan- Meier method. | From the date of first treatment until death or last follow-up, assessed up to 7 years |