Phase II study of PX-866 in recurrent glioblastoma

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

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy
  • Gonanes / administration & dosage
  • Gonanes / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Phosphoinositide-3 Kinase Inhibitors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Gonanes
  • PX-866
  • Phosphoinositide-3 Kinase Inhibitors