Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

Johns Hopkins Medicine

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: benzoylphenylurea

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00016354

NCI-1351 (Other Grant/Funding Number)

U01CA070095 (U.S. NIH Grant/Contract)

J0072 CDR0000068625

P30CA006973 (U.S. NIH Grant/Contract)

JHOC-J0072 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

benzoylphenylurea

Experimental group

Treatment:

Drug: benzoylphenylurea