Temozolomide in Treating Patients With Recurrent High-Grade Glioma

Phase 2

Completed

Conditions: Recurrent Central Nervous System Neoplasm

Interventions: Drug: temozolomide

Registration Number: NCT00619112

Lead Sponsor: University of California, San Francisco

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Temozolomide	temozolomide	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

Primary Outcome Measures

Name	Time	Method
6 Month Progression-free Survival	First day of treatment until progression or until 6 months mark	Efficacy of dose-intense temozolomide treatment schedule, as measured by 6 months progression-free survival

Secondary Outcome Measures

Name	Time	Method
Patients With Tumors With Functional Alterations of the Mismatch Repair (MMR) System	prior to start of study	PCR analysis of tumor tissue for microsatellite instability (MSI). Tissue was obtained during surgeries prior this study.
Patients Progressing After Two First-line Adjuvant Courses of Temozolomide	After two first-line adjuvant courses of temozolomide
Patients Progressing Within 6 Months After 6th Adjuvant Course of Temozolomide	Within 6 months after 6th adjuvant course of temozolomide
Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued	From beginning of voluntarily temozolomide discontinued up to 6 months
Progression-free Survival (PFS) Based on Tumor MGMT (O(6)-Methylguanine-DNA Methyltransferase) Promoter Methylation Status.	First day of treatment until progression or until 6 months mark	Progression-free survival data (obtained for Primary Outcome Measure) was correlated with tumor MGMT (O(6)-methylguanine-DNA methyltransferase) promoter methylation status, obtained from patients as part of the study.
Overall Survival	up to 2 years after treatment