Abstract
EPT-08A PHASE I STUDY OF SINGLE-AGENT PERIFOSINE FOR RECURRENT/REFRACTORY PEDIATRIC CNS AND SOLID TUMORS
Neuro-oncology (Charlottesville, Va.), Vol.18(Suppl 3), pp.iii25-iii25
06/2016
DOI: 10.1093/neuonc/now069.07
Abstract
BACKGROUND: The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. METHODS: We performed a standard 3 + 3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. RESULTS: Twenty-three patients (median age 10 years, range 4-18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3]), neuroblastoma (n = 8), Wilms tumor (n = 1), and Ewing sarcoma (n = 1) were treated. Only one DLT occurred (grade 4 hyperuricemia at dose level 4). The most common grade 3 or 4 toxicity at least possibly related to perifosine was neutropenia (8.7%), with the remaining grade 3 or 4 toxicities (fatigue, hyperglycemia, fever, hyperuricemia, and catheter-related infection) occurring in one patient each. Pharmacokinetics was non-linear at doses above 50 mg/m2/day with significant inter-patient variability, consistent with findings reported in adult studies. One patient with DIPG (dose level 5) and all five patients with high-grade glioma (dose levels 2 and 3) experienced stable disease up to two months. Five subjects with neuroblastoma (dose levels 1 through 4) achieved stable disease which was prolonged (≥11 months) in three. No objective responses were noted. CONCLUSION: The use of this Akt inhibitor was safe and feasible in patients with recurrent/refractory pediatric CNS and solid tumors. An MTD was not defined by the 5 dose levels investigated.
Details
- Title: Subtitle
- EPT-08A PHASE I STUDY OF SINGLE-AGENT PERIFOSINE FOR RECURRENT/REFRACTORY PEDIATRIC CNS AND SOLID TUMORS
- Creators
- Nathan Millard - Memorial Sloan Kettering Cancer CenterOren Becher - Memorial Sloan Kettering Cancer CenterShakeel Modak - Memorial Sloan Kettering Cancer CenterSofia Haque - Memorial Sloan Kettering Cancer CenterIvan Spasojevic - Duke Medical CenterTanya Trippett - Memorial Sloan Kettering Cancer CenterStephen Gilheeney - Memorial Sloan Kettering Cancer CenterYasmin Khakoo - Memorial Sloan Kettering Cancer CenterDavid Lyden - Memorial Sloan Kettering Cancer CenterKevin De Braganca - Memorial Sloan Kettering Cancer CenterJill Kolesar - University of Wisconsin–MadisonJason Huse - Memorial Sloan Kettering Cancer CenterKim Kramer - Memorial Sloan Kettering Cancer CenterIra Dunkel - Cornell University
- Resource Type
- Abstract
- Publication Details
- Neuro-oncology (Charlottesville, Va.), Vol.18(Suppl 3), pp.iii25-iii25
- Publisher
- Oxford University Press
- DOI
- 10.1093/neuonc/now069.07
- ISSN
- 1522-8517
- eISSN
- 1523-5866
- Language
- English
- Date published
- 06/2016
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695788502771
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