Pyrazoloacridine Plus Carboplatin in Treating Patients With Recurrent Glioma

Study Overview
=================
Brief Summary
-----------------
Phase I/II trial to study the effectiveness of pyrazoloacridine plus carboplatin in treating patients who have recurrent glioma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Detailed Description
-----------------
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 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.

Official Title
-----------------
Phase I/II Trial of Pyrazoloacridine and Carboplatin in Patients With Recurrent Glioma

Conditions
-----------------
Brain and Central Nervous System Tumors

Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: pyrazoloacridine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: carboplatin<br> <br> Drug: pyrazoloacridine<br> <br> |
| Experimental: Arm II<br>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. | Drug: carboplatin<br> <br> Drug: pyrazoloacridine<br> <br> |
| Experimental: Arm III<br>Patients receive the same treatment as given in studies 1 and 2 without dose escalation. | Drug: carboplatin<br> <br> Drug: pyrazoloacridine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma