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.
- 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.
- 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
- 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.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival at 1 year
Belgium: Federal Agency for Medicinal Products and Health Products