Benzoylphenylurea in Treating Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00016354
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : August 31, 2012
Last Update Posted : March 25, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: benzoylphenylurea Phase 1

Detailed Description:


  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : March 2001
Actual Primary Completion Date : August 2004
Actual Study Completion Date : September 2006

Arm Intervention/treatment
Experimental: benzoylphenylurea Drug: benzoylphenylurea

Primary Outcome Measures :
  1. Determine Maximum Tolerated Dose of BPU [ Time Frame: 4 weeks (1 course of treatment for each subject) ]
    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 :
  1. Number of Patients With Adverse Events [ Time Frame: every 4 weeks ]
  2. Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU [ Time Frame: 8 weeks ]
  3. Test for Antitumor Activity in Blood and Tissue [ Time Frame: baseline ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed malignancy

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



  • 18 and over

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified


  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3


  • Bilirubin normal
  • SGOT/SGPT normal


  • Creatinine normal
  • Creatinine clearance at least 60 mL/min


  • 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


  • No grade 1 or greater peripheral neuropathy
  • No uncontrolled major seizure disorder
  • No spinal cord compression


  • 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


Biologic therapy:

  • No concurrent immunotherapy
  • No concurrent growth factors during first 2 courses of study
  • Concurrent epoetin alfa allowed


  • At least 28 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No other concurrent chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy


  • 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


  • At least 28 days since prior major surgery


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00016354

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Study Chair: Antonio C. Wolff, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications of Results:
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 at Johns Hopkins Identifier: NCT00016354     History of Changes
Other Study ID Numbers: J0072 CDR0000068625
U01CA070095 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0072 ( Other Identifier: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins )
NCI-1351 ( Other Grant/Funding Number: National Cancer Institute )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: August 31, 2012
Last Update Posted: March 25, 2013
Last Verified: March 2013

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