Conditions: Recurrent Central Nervous System Neoplasm
Keywords: adult glioblastoma adult gliosarcoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult mixed glioma recurrent adult brain tumor
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 60
Healthy volunteers: no

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with recurrent high-grade glioma.

Detailed description:
OBJECTIVES:

Primary

* Determine the efficacy, as measured by 6-month progression-free survival, of a dose-intense temozolomide treatment schedule in patients with recurrent high-grade glioma.

Secondary

* Assess the toxicities of this dose-intense temozolomide.
* Determine the overall survival of patients treated with this dose-intense schedule.
* Determine whether methylation status of the MGMT gene within patients' tumors predicts greater efficacy (progression-free survival), in patients treated on this protocol.
* Determine whether patients' tumors have functional alterations of the mismatch repair (MMR) system by PCR analysis for microsatellite instability (MSI) and whether such alterations may influence outcome in patients treated on this protocol.
* Determine how initial success with temozolomide may influence outcome in recurrent patients treated on this protocol by evaluating patients progressing after two first-line adjuvant courses of temozolomide, patients progressing within 6 months after the 6th adjuvant course of temozolomide, and patients progressing 6 months after temozolomide is voluntarily discontinued.

OUTLINE: Patients receive oral temozolomide once daily on days 1-7 and days 15-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded tissue blocks or unstained paraffin slides from available surgical samples are evaluated for molecular abnormalities in the tumor, including (but not limited to) MGMT status and microsatellite instability.

After completion of study therapy, patients are followed every 3 months for survival.

PROJECTED ACCRUAL: A total of 40 patients with WHO II grade 4 tumors (glioblastoma multiforme \[GBM\]) and 20 patients with WHO II grade 3 tumors (non-GBM) will be accrued for this study.

Arms:
arm 1: single arm trial; Patients treated with temozolomide at a dose of 150mg/m2 daily for seven consecutive days of every other week. One 28-day cycle will include treatment with temozolomide on days 1-7 and days 15-21 with no treatment on days 8-14

Interventions: intervention 1: temozolomide
Intervention descriptions: intervention 1: single arm study

Protocol document: