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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 27, 2014