OBJECTIVES:

• Determine the maximum tolerated dose of pyrazoloacridine plus carboplatin in patients with recurrent glioma.
• Determine the toxic effects of this treatment regimen in these patients.
• Determine the safety of this treatment regimen at the recommended phase II dose in patients not receiving anticonvulsants.
• Determine the efficacy of this treatment regimen in these patients.
• Assess the pharmacokinetics and metabolism of pyrazoloacridine in these patients.
• Assess the response rate, time to progression, and time to death in patients treated with this regimen.

OUTLINE: This is a three-part, dose-escalation, multicenter study. Patients in study 3 are stratified according to concurrent anticonvulsants (yes vs no).

• Study 1: (Study 1 closed as of 03/29/02) Patients receive carboplatin IV over 30 minutes and pyrazoloacridine IV over 3 hours on day 1. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of carboplatin and pyrazoloacridine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

• Study 2: (Study 2 closed as of 03/29/02) Patients receive the same treatment as given in study 1. Dose escalation is performed as in study 1 to determine the MTD in patients not receiving concurrent anticonvulsants.
• Study 3: Patients receive the same treatment as given in studies 1 and 2 without dose escalation.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: Study 1: (Study 1 closed as of 03/29/02)

• A total of 3-21 patients will be accrued for this study within 6-20 months. Study 2: (Study 2 closed as of 03/29/02)
• A total of 3-12 patients will be accrued for this study within 3-18 months.

Study 3:

• A total of 12-37 patients will be accrued for this study within 15 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary brain glioma

  • Diffuse astrocytoma
  • Gliosarcoma
  • Oligodendroglioma
  • Oligoastrocytoma
• Progressive disease after radiotherapy
• Measurable or evaluable disease by MRI or CT

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No other active malignancy
• No other concurrent severe disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No more than 1 prior adjuvant chemotherapy regimen
• No prior polifeprosan 20 with carmustine implant (Gliadel wafer)

• Study 3 only:

  • 1 prior chemotherapy regimen for recurrent disease allowed
  • Prior nonplatinum-containing adjuvant chemotherapy allowed
  • Prior platinum-containing adjuvant chemotherapy allowed if disease progressed at least 6 months after last treatment

Endocrine therapy:

• Non-increasing dose of corticosteroids for at least 1 week allowed

Radiotherapy:

• See Disease Characteristics
• At least 12 weeks since prior radiotherapy
• No prior stereotactic radiosurgery or interstitial brachytherapy unless at least one lesion outside of irradiated area

Surgery:

• No surgical resection since prior radiotherapy or chemotherapy unless evidence of disease progression or lesion outside of treatment site

Other:

• Study 1 only: (Study 1 closed as of 03/29/02)

  • Must be on anticonvulsants that can induce cytochrome P-450 (phenytoin, carbamazepine, barbiturates, or primidone)

• Study 2 only: (Study 2 closed as of 03/29/02)

  • No concurrent anticonvulsants