Radiation Therapy and Temsirolimus or Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Temsirolimus may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. It is not yet
      known whether radiation therapy is more effective when given together with temsirolimus or
      temozolomide in treating patients with glioblastoma.

      PURPOSE: This randomized phase II trial is studying giving radiation therapy together with
      temsirolimus to see how well it works compared with giving radiation therapy together with
      temozolomide in treating patients with newly diagnosed glioblastoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Document the activity profile of temsirolimus by the evaluation of overall survival at 1
           year in patients with newly diagnosed glioblastoma multiforme, without methylation of
           the MGMT gene promoter, treated with temsirolimus before and concomitantly with
           radiotherapy, followed by temsirolimus maintenance therapy.

      Secondary

        -  Investigate safety and tolerability of this therapy regimen in these patients.

        -  Assess progression-free survival and overall survival of these patients.

        -  Assess biomarkers in the tumor tissue relevant to temsirolimus and disease state, and
           their correlation to clinical outcome in these patients.

      OUTLINE: This is a multicenter study. Patients are stratified according to institution, age
      in years (< 50 vs ≥ 50), Karnofsky performance status (PS) (< 80% vs ≥ 80%) OR ECOG PS (0 or
      1 vs 2), and corticosteroid use (yes vs no). Patients are randomized to 1 of 2 treatment
      arms.

        -  Arm I: Within 7 weeks after surgery or open biopsy, patients undergo radiotherapy 5 days
           a week for 6 weeks and receive oral temozolomide concurrently once daily for 6 weeks.
           Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive
           adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide
           repeats every 28 days for up to 12 courses in the absence of disease progression and
           unacceptable toxicity.

        -  Arm II: Within 7 weeks after surgery or open biopsy, patients undergo radiotherapy 5
           days a week for 6 weeks. Patients also receive temsirolimus IV over 30-60 minutes once
           weekly beginning 7 days before initiation of radiotherapy. After completion of
           chemoradiotherapy, patients receive maintenance temsirolimus IV once weekly in the
           absence of disease progression and unacceptable toxicity.

      Frozen tumor biopsies or paraffin-embedded tumor material obtained from surgery or open
      biopsy and blood samples are collected for analysis of molecular markers, determination of
      the methylation status of the MGMT gene promoter (before randomization and at a later time),
      and other studies.

      After completion of study therapy, patients are followed every 3 months.
    

Intervention name(s): temozolomide; temsirolimus
Intervention type(s): Drug; Drug
Intervention description(s): TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.; CCI-779 will be given i.v. once every week at 25 mg. Each treatment should be preceded by supportive medication with a histamine H2-receptor antagonist. A first dose of CCI-779, being 25 mg, will be given on day -7 from RT start.
Intervention MeSH terms: Sirolimus; Temozolomide; Temsirolimus; MTOR Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult glioblastoma