|Canadian Cancer Trials Group MA.32 - A Phase III Randomized Trial of Metformin versus Placebo on Recurrence and Survival in Early Stage Breast Cancer
Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The Canadian Cancer Trials Group (Canadian Cancer Trials Group) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. While maintaining blinding of investigators to outcomes, an analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples was conducted.
Results of the study showed that metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.
Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V. Effect of Metformin vs Placebo on Weight and Metabolic Factors in Canadian Cancer Trials Group MA.32 (ONLINE). J Natl Cancer Inst 107: 2015.
Canadian Cancer Trials Group IND.204 - A Phase II Study of PX-866 in Patients With Glioblastoma Multiforme at Time of First Relapse or Progression
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. The IND.204 investigators performed a phase II study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM.
Thirty-three 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.
The authors reported that 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.
Pitz MW, Eisenhauer EA, MacNeil MV, Thiessen B, Easaw JC, Macdonald DR, Eisenstat DD, Kakumanu AS, Salim M, Chalchal H, Squire J, Tsao MS, Kamel-Reid S, Banerji S, Tu D, Powers J, Hausman DF, Mason WP. Phase II study of PX-866 in recurrent glioblastoma (ONLINE). Neuro-Oncology 2015.