PURPOSE: Loss of PTEN, which is common in glioblastoma multiforme (GBM), results 
in activation of the mammalian target of rapapmycin (mTOR), thereby increasing 
mRNA translation of a number of key proteins required for cell-cycle 
progression. CCI-779 is an inhibitor of mTOR. The primary objectives of this 
study were to determine the efficacy of CCI-779 in patients with recurrent GBM 
and to further assess the toxicity of the drug.
EXPERIMENTAL DESIGN: CCI-779 was administered weekly at a dose of 250 mg 
intravenously for patients on enzyme-inducing anti-epileptic drugs (EIAEDs). 
Patients not on EIAEDs were initially treated at 250 mg; however, the dose was 
reduced to 170 mg because of intolerable side effects. Treatment was continued 
until unacceptable toxicity, tumor progression, or patient withdrawal. The 
primary endpoint was 6-month progression-free survival.
RESULTS: Forty-three patients were enrolled; 29 were not on EIAEDs. The expected 
toxicity profile of increased lipids, lymphopenia, and stomatitis was seen. 
There were no grade IV hematological toxicities and no toxic deaths. One patient 
was progression free at 6 months. Of the patients assessable for response, there 
were 2 partial responses and 20 with stabilization of disease. The median time 
to progression was 9 weeks.
CONCLUSIONS: CCI-779 was well tolerated at this dose schedule; however, there 
was no evidence of efficacy in patients with recurrent GBM. Despite initial 
disease stabilization in approximately 50% of patients, the durability of 
response was short. Because of the low toxicity profile, CCI-779 may merit 
exploration in combination with other modalities.