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

Phase 1/Phase 2
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

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


- 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.

Inclusion Criteria


- 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



- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- Greater than 2 months


- Absolute neutrophil count at least 1500/mm^3

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


- Bilirubin no greater than 1.5 mg/dL

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


- Creatinine no greater than 1.7 mg/dL


- 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


Biologic therapy:

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


- 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


- See Disease Characteristics

- At least 3 months since prior radiotherapy


- Prior surgery allowed


- 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)

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Stuart A. Grossman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

July 1999

Completion Date:

August 2003

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult glioblastoma
  • adult anaplastic astrocytoma
  • adult anaplastic oligodendroglioma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Astrocytoma
  • Brain Neoplasms
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
Emory University Hospital - Atlanta Atlanta, Georgia  30322
University of Pennsylvania Cancer Center Philadelphia, Pennsylvania  19104
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
University of Alabama at Birmingham Comprehensive Cancer Center Birmingham, Alabama  35294-3300
Comprehensive Cancer Center at Wake Forest University Winston-Salem, North Carolina  27157-1082
Henry Ford Hospital Detroit, Michigan  48202
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195