Radiation Therapy (RT) and Temozolomide (TMZ) in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Gliosarcoma; 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 which schedule of
      temozolomide when given together with radiation therapy is more effective in treating
      glioblastoma or gliosarcoma.

      PURPOSE: This randomized phase III trial is studying two different schedules of temozolomide
      to compare how well they work when given together with radiation therapy in treating patients
      with newly diagnosed glioblastoma or gliosarcoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine if dose-intensifying (increasing the "dose-density") the adjuvant temozolomide
           component of the chemoradiation treatment enhances treatment efficacy as measured by
           overall survival of patients with newly diagnosed glioblastoma or gliosarcoma.

      Secondary

        -  Determine if dose-intensifying the adjuvant temozolomide component of the chemoradiation
           treatment enhances treatment efficacy as measured by progression-free survival.

        -  Determine in patients with unmethylated MGMT (O-6-methylguanine-DNA methyltransferase)
           if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment
           enhances treatment efficacy (overall and progression-free survival) compared with
           patients receiving conventional temozolomide dosing.

        -  Determine in patients with methylated MGMT if dose-intensifying the adjuvant
           temozolomide component of the chemoradiation treatment enhances treatment efficacy
           (overall and progression-free survival) compared with patients receiving conventional
           temozolomide dosing.

        -  Determine if there is an association between tumor MGMT gene methylation status and
           treatment response.

        -  Compare and record the toxicities of the conventional and dose-intense chemotherapy
           regimens.

        -  Evaluate whether 6-month progression-free survival is associated with overall survival.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      recursive partitioning analysis class (III vs IV vs V), MGMT gene methylation status
      (methylated vs nonmethylated vs indeterminate), and radiotherapy criteria used (standard vs
      revised European).

      After completion of study treatment, patients are followed every 3 months for 1 year, every 4
      months for 2 years, and then every 6 months thereafter.
    

Intervention name(s): Concurrent temozolomide; Concurrent radiation therapy; 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle; 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle
Intervention type(s): Drug; Radiation; Drug; Drug
Intervention description(s): Daily oral temozolomide (75 mg/m2) up to 49 doses.; 60 Gy in 2 Gy fractions; Oral temozolomide on days 1-5 of a 28-day cycle. Dose starts at 150mg/m2 for first cycle, increases to 200mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.; Oral temozolomide on days 1-21 of a 28-day cycle. Dose starts at 75mg/m2 for first cycle, increases to 100mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.
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