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Clinical Trial
. 2015 Sep;17(9):1270-4.
doi: 10.1093/neuonc/nou365. Epub 2015 Jan 20.

Phase II study of PX-866 in recurrent glioblastoma

Marshall W Pitz  1 , Elizabeth A Eisenhauer  1 , Mary V MacNeil  1 , Brian Thiessen  1 , Jacob C Easaw  1 , David R Macdonald  1 , David D Eisenstat  1 , Ankineedu S Kakumanu  1 , Muhammad Salim  1 , Haji Chalchal  1 , Jeremy Squire  1 , Ming Sound Tsao  1 , Suzanne Kamel-Reid  1 , Shantanu Banerji  1 , Dongsheng Tu  1 , Jean Powers  1 , Diana F Hausman  1 , Warren P Mason  1
Affiliations
Clinical Trial

Phase II study of PX-866 in recurrent glioblastoma

Marshall W Pitz et al. Neuro Oncol. 2015 Sep.

Abstract

Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system in adults. Increased activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway is common. We performed a phase II study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM.

Methods: Patients with histologically confirmed GBM at first recurrence were given oral PX-866 at a dose of 8 mg daily. An MRI and clinical exam were done every 8 weeks. Tissue was analyzed for potential predictive markers.

Results: Thirty-three participants (12 female) were enrolled. Median age was 56 years (range 35-78y). Eastern Cooperative Oncology Group performance status was 0-1 in 29 participants and 2 in the remainder. Median number of cycles was 1 (range 1-8). All participants have discontinued therapy: 27 for disease progression and 6 for toxicity (5 liver enzymes and 1 allergic reaction). Four participants had treatment-related serious adverse events (1 liver enzyme, 1 diarrhea, 2 venous thromboembolism). Other adverse effects included fatigue, diarrhea, nausea, vomiting, and lymphopenia. Twenty-four participants had a response of progression (73%), 1 had partial response (3%, and 8 (24%) had stable disease (median, 6.3 months; range, 3.1-16.8 months). Median 6-month progression-free survival was 17%. None of the associations between stable disease and PTEN, PIK3CA, PIK3R1, or EGFRvIII status were statistically significant.

Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of participants obtained durable stable disease. This study also failed to identify a statistically significant association between clinical outcome and relevant biomarkers in patients with available tissue.

Keywords: PI3K; clinical trial; glioblastoma.

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Figures

Fig. 1.
Fig. 1.
Waterfall plot of radiological response to treatment.
See this image and copyright information in PMC

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