Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00016354
First received: May 6, 2001
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: benzoylphenylurea
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Determine Maximum Tolerated Dose of BPU [ Time Frame: 4 weeks (1 course of treatment for each subject) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Patients With Adverse Events [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
  • Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Test for Antitumor Activity in Blood and Tissue [ Time Frame: baseline ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: March 2001
Study Completion Date: September 2006
Primary Completion Date: August 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: benzoylphenylurea Drug: benzoylphenylurea

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00016354

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Antonio C. Wolff, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
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.

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00016354     History of Changes
Other Study ID Numbers: J0072 CDR0000068625, U01CA070095, P30CA006973, JHOC-J0072, NCI-1351
Study First Received: May 6, 2001
Results First Received: June 11, 2012
Last Updated: March 18, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 23, 2014