Related Experiment Video
Updated: Aug 17, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme
Susan M Chang1, Patrick Wen, Timothy Cloughesy
1University of California, San Francisco, San Francisco, CA 94143, USA. changs@neurosurg.ucsf.edu
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.
Insights
The mTOR inhibitor CCI-779 showed no efficacy in recurrent glioblastoma multiforme (GBM) patients, despite being well-tolerated. While some patients experienced disease stabilization, responses were not durable, suggesting combination therapy may be needed.
Area of Science:
- Oncology
- Pharmacology
Background:
- Loss of PTEN in glioblastoma multiforme (GBM) activates mTOR, promoting cell-cycle progression.
- CCI-779 is an mTOR inhibitor investigated for GBM treatment.
Purpose of the Study:
- To determine the efficacy of CCI-779 in recurrent GBM patients.
- To assess the toxicity profile of CCI-779 in this patient population.
Main Methods:
- Weekly intravenous administration of CCI-779 (250 mg or 170 mg).
- Treatment continued until unacceptable toxicity, progression, or withdrawal.
- Primary endpoint: 6-month progression-free survival.
Main Results:
- Forty-three patients enrolled; 29 not on enzyme-inducing anti-epileptic drugs (EIAEDs).
- Common toxicities included increased lipids, lymphopenia, and stomatitis; no toxic deaths.
- One patient achieved 6-month progression-free survival; 2 partial responses and 20 disease stabilizations observed. Median time to progression was 9 weeks.
Conclusions:
- CCI-779 was well tolerated in recurrent GBM patients at the tested dose.
- No significant efficacy was demonstrated, with short durability of initial disease stabilization.
- Further exploration of CCI-779 in combination therapies may be warranted due to its low toxicity.
