Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins19 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Interventions

benzoylphenylureaDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

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.

Time frame: 4 weeks (1 course of treatment for each subject)

Secondary Outcomes

Number of Patients With Adverse Events

Time frame: every 4 weeks

Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU

Time frame: 8 weeks

Test for Antitumor Activity in Blood and Tissue

Time frame: baseline

Data from ClinicalTrials.gov

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