Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving radiation therapy
      together with temozolomide may kill more tumor cells. It is not yet known whether radiation
      therapy and temozolomide are more effective than radiation therapy alone in treating
      glioblastoma multiforme.

      PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to
      see how well they work compared with radiation therapy alone in treating patients with newly
      diagnosed glioblastoma multiforme.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare overall survival rates in older patients with newly diagnosed glioblastoma
           multiforme treated with short-course radiotherapy with or without temozolomide.

      Secondary

        -  Compare progression-free survival of patients treated with these regimens.

        -  Compare the nature, severity, and frequency of adverse events in patients treated with
           these regimens.

        -  Compare the quality of life of patient treated with these regimens.

        -  Determine the methylation status of the O6-methylguanine-DNA methyltransferase promoter.

      OUTLINE: This is a multicenter, randomized study. Patients are stratified according to
      center, age (65-70 years vs 71-75 years vs ≥ 76 years), ECOG performance status (0-1 vs 2),
      and extent of resection at surgery (biopsy only vs complete or incomplete resection).
      Patients are randomized to 1 of 2 treatment arms.

        -  Arm I: Patients undergo radiotherapy once daily on days 1-5, 8-12, and 15-19 in the
           absence of disease progression or unacceptable toxicity.

        -  Arm II: Patients undergo radiotherapy as in arm I and receive oral temozolomide once
           daily on days 1-25.

      Beginning 4 weeks after completion of radiotherapy and temozolomide, patients receive
      adjuvant oral temozolomide once daily on days 1-5. Treatment with temozolomide alone repeats
      every 28 days for up to 12 months in the absence of disease progression or unacceptable
      toxicity.

      Patients complete quality of life questionnaires at baseline and periodically during study
      treatment.

      Tissue samples are collected at baseline and analyzed for methylation status of the
      O6-methylguanine-DNA methyltransferase promoter.

      After completion of study treatment, patients are followed every 3 months.
    

Intervention name(s): temozolomide; DNA methylation analysis; quality-of-life assessment; Radiation
Intervention type(s): Drug; Genetic; Procedure; Radiation
Intervention description(s): Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate.; A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms; prior to randomization until end of study; Short course radiotherapy
Intervention MeSH terms: Temozolomide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma