Procarbazine in Treating Patients With Recurrent Brain Tumor

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004004
• Other study ID #: CDR0000067214
• Secondary ID: NABTT-9901JHOC-N
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 1, 1999
• Last updated: June 20, 2013
• Start date: July 1999
• Est. completion date: August 2003

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of procarbazine in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme following treatment with radiation therapy.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of oral procarbazine when administered to patients with recurrent glioma receiving or not receiving anticonvulsants metabolized by the P450 hepatic enzyme complex.

• Determine the pharmacokinetics of oral procarbazine, including any effects of hepatic enzyme inducing drugs, in these patients.

• Assess the response rate to procarbazine in these patients.

• Evaluate this regimen in terms of overall survival and duration of disease free survival in these patients.

• Evaluate the toxicity of this regimen in these patients.

OUTLINE: Phase I of this study is a dose escalation study. Patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs no drugs or modest-induction drugs).

• Phase I: Patients receive oral procarbazine once daily for 5 days. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of oral procarbazine until the maximum tolerated dose (MTD) is determined.

• Phase II: Once the MTD is determined, patients receive procarbazine as in Phase I.

Patients are followed every 2 months until death.

PROJECTED ACCRUAL: A total of 24-35 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: August 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven malignant glioma of one of the following types:

• Anaplastic astrocytoma

• Anaplastic oligodendroglioma

• Glioblastoma multiforme

• Progressive or recurrent disease after radiotherapy with or without chemotherapy

• Measurable disease by serial MR or CT

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Greater than 2 months

Hematopoietic:

• Absolute neutrophil count at least 1500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

• SGPT/SGOT no greater than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.7 mg/dL

Other:

• No serious concurrent infection

• No other illness that would preclude study

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prior malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF) during the first course

Chemotherapy:

• See Disease Characteristics

• No more than 1 prior chemotherapy regimen

• At least 3 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas)

• No more than 2 prior courses of carmustine or lomustine and no greater than 460 mg/m2 or 220 mg/m2, respectively

• No prior procarbazine

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

• At least 3 months since prior radiotherapy

Surgery:

• Prior surgery allowed

Other:

• Recovered from toxicity of prior therapy

• At least 10 days since prior anticonvulsants for patients in Arm II

• No concurrent investigational agents

• No concurrent ethanol, ephedrine, isoproterenol, epinephrine, tricyclic antidepressants, paragyliline, narcotic analgesics, antihistamines, phenothiazines, hypotensives, or barbiturates

• At least 14 days since prior antidepressants (e.g., SSRI and/or MAO inhibitor)

• Must avoid foods high in tyramine (i.e., dark beer, wine, yogurt, cheese, bananas)

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• procarbazine hydrochloride

Locations

Country	Name	City	State
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
New Approaches to Brain Tumor Therapy Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

He X, Batchelor TT, Grossman S, Supko JG; New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. Determination of procarbazine in human plasma by liquid chromatography with electrospray ionization mass spectrometry. J Chromatogr B Analyt Technol Bi — View Citation