Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	JHOC-J0072 NCI-1351, NCT00016354, P1351

Objectives

1. Determine the maximum tolerated dose of benzoylphenylurea in patients with advanced solid tumors.
2. Evaluate the acute and chronic toxicity profile of this regimen in these patients.
3. Evaluate the pharmacokinetics and metabolites of this regimen and any potential correlation with pharmacodynamic effects in these patients.
4. Determine the antitumor activity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignancy
  • Metastatic or unresectable
  • No effective standard curative or palliative measures exist
• No known CNS or brain metastasis

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

Approximately 18-24 patients will be accrued for this study.

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.

Messersmith WA, Rudek MA, Baker SD, et al.: Phase I study of continuous weekly dosing of dimethylamino benzoylphenylurea (BPU) in patients with solid tumours. Eur J Cancer 43 (1): 78-86, 2007.[PUBMED Abstract]

Messersmith WA, Baker SD, Donehower RC, et al.: Phase I study of continuous weekly dosing of dimethyl benzoylphenylurea (BPU) in patients with solid tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-815, 2003.

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Antonio Wolff, MD, Protocol chair		Ph: 410-614-4192 Email: awolff@jhmi.edu

Registry Information
Official Title		Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients with Solid Tumors Not Responding to Conventional Therapy
Trial Start Date		2001-03-29
Registered in ClinicalTrials.gov		NCT00016354
Date Submitted to PDQ		2001-03-28
Information Last Verified		2004-10-24
NCI Grant/Contract Number		P30-CA06973, U01-CA70095

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