Metformin, Neo-adjuvant Temozolomide and Hypo- Accelerated Radiotherapy Followed by Adjuvant TMZ in Patients With GBM

Summary

Participation Requirements

Description

Metformin, a drug with a very safe toxicity profile, is an attractive molecule to be tested in patients with newly diagnosed GBM in a phase I clinical trial. This is based on its potential to inhibit the proliferation of GBM CSCs through its mechanism of action which is similar to IR and TMZ. Metfor...

Metformin, a drug with a very safe toxicity profile, is an attractive molecule to be tested in patients with newly diagnosed GBM in a phase I clinical trial. This is based on its potential to inhibit the proliferation of GBM CSCs through its mechanism of action which is similar to IR and TMZ. Metformin, IR, and TMZ stimulate AMPK leading to the subsequent inhibition of cellular proliferation. Therefore, it is hypothesized that the addition of Metformin to concomitant IR and TMZ may increase the efficiency of IR and TMZ, which are currently considered as the standard of care for patients with GBM. In addition, Metformin lowers blood glucose levels, and subsequently reduces the insulin and Insulin-Growth-factors which are growth-promoting factors with a direct impact on GBM cellular proliferation and invasion. Metformin may improve the outcomes of patients with GBM when added to current treatment consisting of maximal safe surgical resection followed by neo-adjuvant TMZ and concomitant accelerated hypofractionated limited-margin XRT followed by adjuvant TMZ. Our Neuro-Oncology group at McGill University reviewed the results of an ongoing Phase II study in patients with GBM. A group of 33 patients were treated according to protocol, and with a median follow-up of 11 months, the median survival was 17.5 months which compares favourably to current results from standard treatment with a beneficial 2-week shortening of the XRT treatment time. This is a phase II clinical trial to assess the feasibility and overall toxicity of adding Metformin to Neoadjuvant Temozolomide followed by concomitant Temozolomide and accelerated hypofractionated limited-margin radiotherapy and followed by adjuvant Temozolomide in patients with newly diagnosed GBM. It is expected that the proposed study treatment will improve the median survival from current values of 20 months (current MUHC Neo-adjuvant Phase 2 data) to 25 months. This means an improved outcome of 25%. Using one-tailed statistics, and with a power of 0.8 and an alpha of 0.05, the sample size for this Phase II trial will be 50 patients.

Tracking Information