Benzoylphenylurea in Treating Patients With Advanced Cancer

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00010205
First received: February 2, 2001
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

This phase I trial is studying the side effects and best dose of benzoylphenylurea in treating patients with advanced cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die


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

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial Of Benzoylphenylurea (NSC#639829) In Advanced Malignancy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) defined as the highest dose level where 0/6 or 1/6 patients experience dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0 [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • DLT defined as grade 3 or worse non-hematologic and sustained (> 5 days) grade 3 hematologic toxicity or grade 4 hematologic toxicity of any duration, and the moderate toxicity is grade 2 toxicity as assessed by CTCAE version 3.0 [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of benzoylphenylurea [ Time Frame: At baseline, at 0.5, 1.0, 1.5, 2, 4, 6, 8, 24, 48, 72, and 96 hours (weeks 1 and 6) ] [ Designated as safety issue: No ]
    Relationships between drug exposure and toxicity, efficacy, and biological endpoints will be explored using univariate and multivariate analysis techniques.


Secondary Outcome Measures:
  • Response (complete and partial response) rate [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Response rate will be evaluated for all patients with measurable disease and will be obtained by dividing the total number of responses by all patients with measurable disease and reported with 95% confidence intervals.

  • Survival [ Time Frame: From the date of first treatment until death or last follow-up, assessed up to 7 years ] [ Designated as safety issue: No ]
    The median and landmark survivals will be estimated utilizing the Kaplan- Meier method.


Enrollment: 30
Study Start Date: December 2000
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (benzoylphenylurea)
Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.
Drug: benzoylphenylurea
Given orally
Other Name: BPU
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

OBJECTIVES:

I. Determine the dose-limiting toxicity and the maximum tolerated dose of benzoylphenylurea in patients with advanced malignancy.

II. Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-30 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

Inclusion Criteria:

  • Histologically confirmed malignancy

    • Metastatic or unresectable
    • No standard curative or palliative measures exist or are ineffective
  • Brain metastases allowed provided 1 of the following criteria is met:

    • Lesions were previously treated with surgery, radiotherapy, or chemotherapy AND are currently asymptomatic AND no steroid therapy or antiseizure medication within the past 2 weeks
    • Untreated, asymptomatic metastases AND no requirement for steroid therapy or antiseizure medication
  • Performance status - ECOG 0-2
  • More than 12 weeks
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin normal
  • SGOT/SGPT no greater than 2.5 times upper limit of normal
  • Albumin at least 3.0 mg/dL
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • No prior allergic reactions to compounds of similar chemical or biologic composition to benzoylphenylurea
  • No neuropathy greater than grade 1
  • No other uncontrolled medical or psychiatric illness that would preclude study compliance
  • No ongoing or active infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Prior immunotherapy allowed
  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
  • At least 2 weeks since steroids for CNS disease
  • At least 4 weeks since prior radiotherapy and recovered
  • Prior surgery allowed
  • At least 2 weeks since antiseizure medications for CNS disease
  • More than 7 days since prior CYP3A4 or CYP2D6 inhibitors
  • More than 7 days since prior CYP3A4 inducers
  • No concurrent CYP3A4 or CYP2D6 inhibitors
  • No concurrent CYP3A4 inducers
  • No other concurrent investigational agents
  • No concurrent combination anti-retroviral therapy for HIV
  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: NCT00010205

Locations
United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
Sponsors and Collaborators
Investigators
Principal Investigator: Martin Edelman University of Maryland Greenebaum Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00010205     History of Changes
Other Study ID Numbers: NCI-2012-02375, UMGCC 0038, U01CA069854, CDR0000068455
Study First Received: February 2, 2001
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on August 21, 2014