Reference Detail

Ref Type

Journal Article

PMID

(31325145)

Authors

Kaley TJ, Panageas KS, Mellinghoff IK, Nolan C, Gavrilovic IT, DeAngelis LM, Abrey LE, Holland EC, Lassman AB

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of neuro-oncology	144	2	2019 Sep	403-407	J Neurooncol

URL

Abstract Text

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).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.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).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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Perifosine	Perifosine	3	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Perifosine		KRX-0401\|NSC-639966	Akt Inhibitor (Pan) 21	Perifosine (KRX-0401) is a synthetic alkylphospholipid that inhibits AKT resulting in apoptotic induction and antitumor activity (PMID: 16418332, PMID: 28864978, PMID: 31325145).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References