Conditions: Glioblastoma Gliosarcoma
Keywords: GBM Brain tumor Erlotinib Sirolimus Glioblastoma multiforme Glioblastoma Gliosarcoma3 Tarceva Rapamune
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 32
Healthy volunteers: no

Brief summary:
Primary objective:

To determine the 6-month progression free survival of patients with recurrent glioblastoma multiforme (GBM) treated with Erlotinib plus Sirolimus.

Secondary objectives:

To further define the safety and tolerability of Erlotinib plus Sirolimus when administered to patients with recurrent GBM; and to evaluate progression free survival, radiographic response and overall survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus.

Detailed description:
The primary objective of this study will be to determine the 6-month progression free survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus.

This is an exploratory, single-arm, phase II study designed to assess the anti-tumor activity of a combinatorial regimen consisting of Erlotinib plus Sirolimus among patients with recurrent GBM. The combinatorial regimen of Erlotinib plus Sirolimus is rationally designed to simultaneously inhibit upstream (EGFR) and downstream (mTOR) mediators of Phosphatidylinositide 3-kinase/Protein Kinase B (PI3/AKT) signaling. In a recently completed phase I study, we determined that an EGFR inhibitor (Gefitinib) can be safely combined with Sirolimus at dose levels that are routinely used in the monotherapy setting. Therefore, the primary endpoint of this study is the probability of progression-free survival at 6 months among recurrent GBM patients treated with standard doses of Erlotinib plus Sirolimus. An important secondary objective is to further assess the safety of Erlotinib and Sirolimus for patients with recurrent GBM.

Arms:
arm 1: Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent Cytochrome P450, family 3 (CY3PA)-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS.

Interventions: intervention 1: Erlotinib + sirolimus
Intervention descriptions: intervention 1: Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of oral erlotinib and 5mg of oral sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of oral erlotinib and 10 mg of oral sirolimus for patients on concurrent EIAEDS.

Protocol document: