Clinical Trial Finder

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.

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: 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:

• - 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

OBJECTIVES:

• I. Determine the maximum tolerated dose of pyrazoloacridine plus carboplatin in patients with recurrent glioma.

• II. Determine the toxic effects of this treatment regimen in these patients.

• III. Determine the safety of this treatment regimen at the recommended phase II dose in patients not receiving anticonvulsants.

• IV. Determine the efficacy of this treatment regimen in these patients.

• V. Assess the pharmacokinetics and metabolism of pyrazoloacridine in these patients.

• VI. 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.#46;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: A total of 3-21 patients will be accrued for this study within 6-20 months. Study 2: 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.

Arms

Experimental: Arm I

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.

Experimental: Arm II

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.

Experimental: Arm III

Patients receive the same treatment as given in studies 1 and 2 without dose escalation.

Interventions

Drug: - carboplatin

Drug: - pyrazoloacridine