Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Procarbazine in Treating Patients With Recurrent Brain Tumor

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI NABTT-9901 JHOC-NABTT-9901, NCT00004004

Objectives

1. 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.
2. Determine the pharmacokinetics of oral procarbazine, including any effects of hepatic enzyme inducing drugs, in these patients.
3. Assess the response rate to procarbazine in these patients.
4. Evaluate this regimen in terms of overall survival and duration of disease free survival in these patients.
5. Evaluate the toxicity of this regimen in these patients.

Entry 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

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)

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Greater than 2 months

Hematopoietic:

• Absolute neutrophil count at least 1500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

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.

He X, Batchelor TT, Grossman S, et al.: Determination of procarbazine in human plasma by liquid chromatography with electrospray ionization mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 799 (2): 281-91, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Stuart Grossman, MD, Protocol chair		Ph: 410-955-8837 Email: Grossman@jhmi.edu

Registry Information
Official Title		A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas
Trial Start Date		1999-07-21
Registered in ClinicalTrials.gov		NCT00004004
Date Submitted to PDQ		1999-07-22
Information Last Verified		2007-05-18
NCI Grant/Contract Number		CA006973, CA062475

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