Radiation Therapy and Concurrent Plus Adjuvant Temsirolimus (CCI-779) Versus Chemo-Irradiation With Temozolomide in Newly Diagnosed Glioblastoma Without Methylation of the MGMT Gene Promoter - A Randomized Multicenter, Open-Label, Phase II Study.
Overview
- Phase
- Phase 2
- Intervention
- temozolomide
- Conditions
- Brain and Central Nervous System Tumors
- Sponsor
- European Organisation for Research and Treatment of Cancer - EORTC
- Enrollment
- 111
- Locations
- 13
- Primary Endpoint
- Overall survival at 1 year
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Temozolomide
TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.
Intervention: temozolomide
Temsirolimus
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: temsirolimus
Outcomes
Primary Outcomes
Overall survival at 1 year
Time Frame: 1 year
Secondary Outcomes
- Percentages of worst Adverse Events or Laboratory Event grades as measured by CTCAEs Version 4.0 criteria(end of trial)
- Progression-free survival (PFS) probability at 6 months and at 12 months, and overall survival (OS) probability at 2 years(end of trial)
- Correlation between biomarkers relevant to temsirolimus and PFS and OS(end of trial)