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

NCT02780024 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MUHC ID: 4315
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma Multiforme

Keywords

Neo-Adjuvant Metformin; Neo-Adjuvant Temozolomide; Temozolomide and accelerated hypofractionation; Metformin and accelerated hypofractionation; Adjuvant Temozolomide; Adjuvant Metformin

Outcome Measures

Primary Outcomes (1)

• Number of patients completing the study treatment

  To determine overall survival

  At one year

Secondary Outcomes (1)

• To assess toxicity of the regimen

  One year

Study Arms (1)

Registered one arm study

EXPERIMENTAL

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.

Drug: Metformin

Interventions

Metformin DRUG

Metformin,

Also known as: Glucophage

Registered one arm study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 years or older
• Histological confirmation of supra-tentorial GBM
• KPS \> 60
• Neurological function 0 or 1
• Adequate bone marrow as defined below:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3. Platelets ≥ 100,000 cells/mm3 Hemoglobin ≥ 10 g/dl.
• Adequate renal function, as defined below:
• Creatinine clearance of \>60 ml/min/1.73m2 (using the Cockcroft Gault equation for eGFR) within 14 days prior to study registration
• Adequate hepatic function, as defined below:
• Bilirubin of 1.7 to 18.9 umol/L within 14 days prior to study registration
• ALT ≤ 3 x normal range within 14 days prior to study registration
• Neo-adjuvant TMZ and Metformin to start within 4 weeks of surgery
• Concomitant TMZ and Metformin and accelerated Hypofractionated EBRT to start at least 2 weeks after adjuvant TMZ starting date, and no later than five weeks from surgery.
• Surgical diagnosis/intervention may include: partial or near total resection
• Patients must have recovered from the effects of surgery, postoperative infection and other complications before study registration.

You may not qualify if:

• Diabetic patients both type I and type II.
• No tissue provided for MGMT promoter methylation status determination.
• Margin of contrast-enhanced residual mass closer than 15 mm from the optic chiasm or optic nerves.
• Prior invasive malignancy (except for non-melanoma skin cancer) unless disease free for ≥ 3 years
• Recurrent or multifocal GBM.
• Prior chemotherapy or radio-sensitizers for cancers of the head and neck region; prior chemotherapy for a different cancer is allowable.
• Severe, active co-morbidity, defined as follows:
• Acute or chronic renal failure.
• Unstable angina and/or congestive heart failure requiring hospitalization
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition.
• Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• Pregnant or lactating women, due to possible adverse effects on the developing foetus or infant due to study drug.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

Montreal Neurological Institute - McGill University Health Centre

Montreal, Quebec, H3A 2B4, Canada

Location

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MeSH Terms

Conditions

Glioblastoma

Interventions

Metformin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• George Shenouda, M.D.

  Radiation Oncologist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 23, 2016
• Study Start: March 1, 2015
• Primary Completion: October 20, 2021
• Study Completion (Estimated): February 28, 2027
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)