A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas
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.
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)
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Stuart A. Grossman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000067214
NCT ID:
NCT00004004
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
Name | Location |
|---|---|
| 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 |
