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Investigational New Drugs

, Volume 23, Issue 4, pp 357–361 | Cite as

Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme

  • Susan M. Chang
  • Patrick Wen
  • Timothy Cloughesy
  • Harry Greenberg
  • David Schiff
  • Charles Conrad
  • Karen Fink
  • H. Ian Robins
  • Lisa De Angelis
  • Jeffrey Raizer
  • Kenneth Hess
  • Ken Aldape
  • Kathleen R. Lamborn
  • John Kuhn
  • Janet Dancey
  • Michael D. Prados
  • North American Brain Tumor Consortium and the National Cancer Institute
Article

Abstract

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.

Keywords

chemotherapy CCI-779 rapamycin glioblastoma multiforme recurrent efficacy 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Susan M. Chang
    • 1
  • Patrick Wen
    • 2
  • Timothy Cloughesy
    • 3
  • Harry Greenberg
    • 4
  • David Schiff
    • 5
  • Charles Conrad
    • 6
  • Karen Fink
    • 7
  • H. Ian Robins
    • 8
  • Lisa De Angelis
    • 9
  • Jeffrey Raizer
    • 9
  • Kenneth Hess
    • 6
  • Ken Aldape
    • 6
  • Kathleen R. Lamborn
    • 1
  • John Kuhn
    • 10
  • Janet Dancey
    • 11
  • Michael D. Prados
    • 1
  • North American Brain Tumor Consortium and the National Cancer Institute
  1. 1.University of CaliforniaSan Francisco
  2. 2.Dana Farber Cancer InstituteUSA
  3. 3.University of CaliforniaLos Angeles
  4. 4.University of MichiganUSA
  5. 5.University of VirginiaUSA
  6. 6.MD Anderson Cancer CenterUSA
  7. 7.University of TexasSouthwestern
  8. 8.Unversity of WisconsinUSA
  9. 9.Memorial Sloan Kettering Cancer CenterUSA
  10. 10.University of TexasSan Antonio
  11. 11.Cancer Therapy Evaluation ProgramNational Cancer InstituteUSA

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