Phase II study of PX-866 in recurrent glioblastoma. Issue 9 (20th January 2015)

• Record Type: Journal Article
• Authors: Pitz, Marshall W.; Eisenhauer, Elizabeth A.; MacNeil, Mary V.; Thiessen, Brian; Easaw, Jacob C.; Macdonald, David R.; Eisenstat, David D.; Kakumanu, Ankineedu S.; Salim, Muhammad; Chalchal, Haji; Squire, Jeremy; Tsao, Ming Sound; Kamel-Reid, Suzanne; Banerji, Shantanu; Tu, Dongsheng; Powers, Jean; Hausman, Diana F.; Mason, Warren P.
• Is Part Of: Neuro-oncology. Volume 17:Issue 9(2015:Sep.)
• Page Start: 1270
• Page End: 1274
• Publication Date: 2015-01-20
• Subjects: clinical trial -- glioblastoma -- PI3K; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/nou365
• Languages: English
• ISSNs: 1522-8517

Abstract

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.