Metformin, Neo-adjuvant Temozolomide and Hypo- Accelerated Radiotherapy Followed by Adjuvant TMZ in Patients With GBM
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|ClinicalTrials.gov Identifier: NCT02780024|
Recruitment Status : Active, not recruiting
First Posted : May 23, 2016
Last Update Posted : September 5, 2021
Glioblastoma Multiforme is one of the most common, and unfortunately one of the most aggressive brain tumors in adults with most of the patients recurring and dying of the disease with a median survival of 16 months from diagnosis.
Current treatment for patients with newly diagnosed Glioblastoma Multiforme (GBM) is safe maximal surgical resection followed by concomitant conventional Radiotherapy (RT) delivered in 6 weeks + Temozolomide (TMZ) followed by TMZ for 6 to 12 cycles.
Recent scientific research has shown that Metformin, a common drug used to treat diabetes mellitus, may improve the results of the treatment in patients with a variety of cancers, such as breast, colon, and prostate cancer. Metformin is an attractive and safe medication to be used in this group of patients because of its very low toxicity.
In our center the investigators have been using TMZ for 2 weeks prior to a short course (4 weeks) of RT which equivalent to the standard RT of 6 weeks. Temozolomide is used 2 weeks before RT + TMZ, and this is followed by the 6 to 12 cycles of TMZ. Our results are quiet encouraging with a median survival of 20 months, and acceptable toxicity.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Drug: Metformin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Metformin and Neo-adjuvant Temozolomide and Hypofractionated Accelerated Limited-margin Radiotherapy Followed by Adjuvant Temozolomide in Patients With Glioblastoma Multiforme (M-HARTT STUDY)|
|Study Start Date :||March 2015|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2023|
Experimental: Registered one arm study
Two weeks of neo-adjuvant Metformin+Temozolomide followed by accelerated hypofractionation using an IMRT technique+TMZ & Metformin followed by TMZ, and Metformin as adjuvant component.
Other Name: Glucophage
- Number of patients completing the study treatment [ Time Frame: At one year ]To determine overall survival
- To assess toxicity of the regimen [ Time Frame: One year ]Toxicity will be assessed and graded according to CTCAE-V4
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02780024
|Montreal Neurological Institute - McGill University Health Centre|
|Montréal, Quebec, Canada, H3A 2B4|
|Principal Investigator:||George Shenouda, M.D.||Radiation Oncologist|