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Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy


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.

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine Maximum Tolerated Dose of BPU

Outcome Description:

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.

Outcome Time Frame:

4 weeks (1 course of treatment for each subject)

Safety Issue:

Yes

Principal Investigator

Antonio C. Wolff, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

J0072 CDR0000068625

NCT ID:

NCT00016354

Start Date:

March 2001

Completion Date:

September 2006

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410