Phase II Trial of Erlotinib Plus Sirolimus for Patients With Recurrent Malignant Glioma Multiforme
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.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
6-month Progression-free Survival (PFS)
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
David Reardon, MD
Duke University Health System
United States: Institutional Review Board
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