Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00016354

Last Updated: 2013-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-03-31
• Study Completion Date: 2006-09-30

Brief Summary

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

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

benzoylphenylurea

Group Type: EXPERIMENTAL

benzoylphenylurea

Intervention Type: DRUG

Interventions

benzoylphenylurea

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio C. Wolff, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

Messersmith WA, Rudek MA, Baker SD, Zhao M, Collins C, Colevas AD, Donehower RC, Carducci MA, Wolff AC. Phase I study of continuous weekly dosing of dimethylamino benzoylphenylurea (BPU) in patients with solid tumours. Eur J Cancer. 2007 Jan;43(1):78-86. doi: 10.1016/j.ejca.2006.09.006. Epub 2006 Nov 3.

Reference Type: RESULT

PMID: 17084620 (View on PubMed)

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.

Reference Type: RESULT

Other Identifiers

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0072

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-1351

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

J0072 CDR0000068625

Identifier Type: -

Identifier Source: org_study_id