Benzoylphenylurea in Treating Patients With Advanced Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00010205
• Other study ID #: NCI-2012-02375
• Secondary ID: UMGCC 0038U01CA0
• Status: Terminated
• Phase: Phase 1
• First received: February 2, 2001
• Last updated: January 24, 2013
• Start date: December 2000

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• benzoylphenylurea
Given orally

Other:
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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)	No
Secondary	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	No
Secondary	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	No