Gimatecan in Treating Patients With Recurrent or Progressive Primary Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gimatecan, work in different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I/II trial is studying the side effects and best dose of gimatecan in treating patients with recurrent or progressive primary malignant glioma.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose (MTD) of gimatecan in patients with recurrent or progressive primary malignant glioma treated with or without concurrent enzyme-inducing anticonvulsant drugs. Determine whether this drug has sufficient activity to warrant further development in these patients. (phase II) Secondary Determine the qualitative and quantitative toxic effects of this drug in these patients. Determine the pharmacokinetic behaviors of this drug in these patients. Correlate the principal toxic effects with the pertinent pharmacokinetic parameters of this drug in these patients. Determine the antitumor activity of this drug in these patients. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients are stratified according to the concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no). Phase I: Patients receive oral gimatecan once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gimatecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive gimatecan as in phase I at the MTD. Patients are followed for at least 1 month and then every 2 months thereafter. PROJECTED ACCRUAL: Approximately 30-83 patients (30-42 for phase I [15-21 per stratum] and 21-41 for phase II) will be accrued for this study within 24 months.

Official Title
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Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: gimatecan


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or anaplastic oligodendroglioma) Recurrent or progressive primary CNS neoplasm by contrast-enhanced MRI Tumor progression after prior surgery, radiotherapy, or chemotherapy Measurable or evaluable disease Failed prior standard curative or palliative therapy (phase I only) PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy At least 3 months Hematopoietic Absolute neutrophil count ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic SGPT and SGOT ≤ 1.5 times upper limit of normal (ULN) (3 times ULN if liver metastases are present) Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present) Bilirubin normal Renal Creatinine ≤ 1.5 times ULN Cardiovascular No myocardial infarction with the past year No heart failure (including cardiac insufficiency controlled by digitalis and diuretics) No irreversible arrhythmias requiring permanent medication No uncontrolled hypertension Gastrointestinal No gastrointestinal dysfunction that would alter absorption or motility, such as any of the following: Active peptic ulcer Inflammatory bowel disease Known intolerance to lactose Malabsorption syndromes Intestinal sub-occlusion Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No active infection No mentally incapacitated patients No other concurrent severe disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) No more than 1 prior chemotherapy regimen No other concurrent chemotherapy Endocrine therapy Concurrent corticosteroids allowed if dose stable for the past 2 weeks No concurrent hormonal therapy Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery See Disease Characteristics At least 3 weeks since prior surgical resection No prior gastrointestinal surgery that would affect drug absorption Other More than 4 weeks since prior participation in any other investigational drug study More than 72 hours since prior systemic antibiotics No concurrent H2 antagonists, antacids, or proton pump inhibitors If any of these therapies are necessary, ≥ 3 hours must elapse after gimatecan administration No other concurrent anticancer therapy No other concurrent investigational drugs No other concurrent immunosuppressive agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gimatecan|nan|

What is the study measuring?
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Primary Outcome Measures

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

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