Benzoylphenylurea in Treating Patients With Advanced Cancer

Phase I Trial Of Benzoylphenylurea (NSC#639829) In Advanced Malignancy

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

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: pharmacological study; Drug: benzoylphenylurea

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201-1595
      • University of Maryland Greenebaum Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: benzoylphenylurea; Given orally; Other Names: BPU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		8 weeks
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		8 weeks
Pharmacokinetics of benzoylphenylurea	Relationships between drug exposure and toxicity, efficacy, and biological endpoints will be explored using univariate and multivariate analysis techniques.	At baseline, at 0.5, 1.0, 1.5, 2, 4, 6, 8, 24, 48, 72, and 96 hours (weeks 1 and 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response (complete and partial response) rate	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.	Up to 7 years
Survival	The median and landmark survivals will be estimated utilizing the Kaplan- Meier method.	From the date of first treatment until death or last follow-up, assessed up to 7 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Martin Edelman, University of Maryland Greenebaum Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2000
• Primary Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 25, 2013
• Last Update Submitted That Met QC Criteria: January 24, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Other Study ID Numbers: NCI-2012-02375; UMGCC 0038; U01CA069854 (U.S. NIH Grant/Contract); CDR0000068455 (Registry Identifier: PDQ (Physician Data Query))