Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma Journal Article

Authors: Kaley, T. J.; Panageas, K. S.; Mellinghoff, I. K.; Nolan, C.; Gavrilovic, I. T.; DeAngelis, L. M.; Abrey, L. E.; Holland, E. C.; Lassman, A. B.
Article Title: Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma
Abstract: Purpose: Perifosine (PRF) is an oral alkylphospholipid with antineoplastic effects and reasonable tolerability. It inhibits signaling through the PI3/AKT axis and other cascades of biologic importance in glioblastoma, and has promising pre-clinical activity in vitro and in vivo. Therefore, we conducted a phase II open-label single-arm clinical trial of perifosine for patients with recurrent glioblastoma (GBM). Methods: We planned to accrue up to 30 adults with recurrent GBM with a minimum Karnofsky Performance Status of 50 following radiotherapy but without other restrictions on the number or types of prior therapy. Concurrent p450 stimulating hepatic enzyme inducing anticonvulsants were prohibited. Patients were treated with a loading dose of 600 mg PRF (in 4 divided doses on day 1) followed by 100 mg daily until either disease progression or intolerable toxicity. The primary endpoint was the 6-month progression free survival (PFS6) rate, with at least 20% considered promising. Accrual was continuous but if 0 of the first 12 patients with GBM reached PFS6, then further accrual would terminate for futility. Patients with other high grade gliomas were accrued concurrently to an exploratory cohort. Results: Treatment was generally well tolerated; gastrointestinal toxicities were the most common side effects, although none resulted in treatment discontinuation. However, there was limited to no efficacy in GBM (n = 16): the PFS6 rate was 0%, median PFS was 1.58 months [95% CI (1.08, 1.84)], median overall survival was 3.68 months [95% CI (2.50, 7.79)], with no radiographic responses. There was a confirmed partial response in one patient with anaplastic astrocytoma (n = 14). Conclusions: PRF is tolerable but ineffective as monotherapy for GBM. Preclinical data suggests synergistic effects of PRF in combination with other approaches, and further study is ongoing. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: clinical trial; chemotherapy; glioblastoma; akt; phase ii; perifosine
Journal Title: Journal of Neuro-Oncology
Volume: 144
Issue: 2
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2019-09-01
Start Page: 403
End Page: 407
Language: English
DOI: 10.1007/s11060-019-03243-7
PUBMED: 31325145
PROVIDER: scopus
PMCID: PMC7493746
Notes: Article -- Export Date: 30 August 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Andrew Lassman
    111 Lassman
  2. Eric Holland
    224 Holland
  3. Thomas Kaley
    128 Kaley
  4. Lauren E Abrey
    276 Abrey
  5. Katherine S Panageas
    430 Panageas
  6. Craig Nolan
    51 Nolan