Procarbazine in Treating Patients With Recurrent Brain Tumor

NCT ID: NCT00004004

Last Updated: 2013-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-07-31
• Study Completion Date: 2003-08-31

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/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.

Detailed 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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

procarbazine hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

New Approaches to Brain Tumor Therapy Consortium

OTHER

Sponsor Role: lead

Principal Investigators

Stuart A. Grossman, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 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

Countries

United States

References

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 Biomed Life Sci. 2004 Jan 25;799(2):281-91. doi: 10.1016/j.jchromb.2003.10.061.

Reference Type: RESULT

PMID: 14670747 (View on PubMed)

Other Identifiers

NABTT-9901

Identifier Type: -

Identifier Source: secondary_id

JHOC-NABTT-9901

Identifier Type: -

Identifier Source: secondary_id

CDR0000067214

Identifier Type: -

Identifier Source: org_study_id