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 :
Recruiting
First Posted : May 23, 2016
Last Update Posted : November 3, 2020
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Tracking Information | |||||||||
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First Submitted Date ICMJE | May 20, 2015 | ||||||||
First Posted Date ICMJE | May 23, 2016 | ||||||||
Last Update Posted Date | November 3, 2020 | ||||||||
Study Start Date ICMJE | March 2015 | ||||||||
Estimated Primary Completion Date | December 2020 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Number of patients completing the study treatment [ Time Frame: At one year ] To determine overall survival
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Original Primary Outcome Measures ICMJE |
Percent of patients completing the study treatment [ Time Frame: At one year ] To determine overall survival
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Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
To assess toxicity of the regimen [ Time Frame: One year ] Toxicity will be assessed and graded according to CTCAE-V4
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Metformin, Neo-adjuvant Temozolomide and Hypo- Accelerated Radiotherapy Followed by Adjuvant TMZ in Patients With GBM | ||||||||
Official Title ICMJE | Metformin and Neo-adjuvant Temozolomide and Hypofractionated Accelerated Limited-margin Radiotherapy Followed by Adjuvant Temozolomide in Patients With Glioblastoma Multiforme (M-HARTT STUDY) | ||||||||
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. |
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Detailed 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. 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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Glioblastoma Multiforme | ||||||||
Intervention ICMJE | Drug: Metformin
Metformin,
Other Name: Glucophage
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Study Arms ICMJE | 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.
Intervention: Drug: Metformin
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
50 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 2022 | ||||||||
Estimated Primary Completion Date | December 2020 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Absolute neutrophil count (ANC) ≥ 1500 cells/mm3. Platelets ≥ 100,000 cells/mm3 Hemoglobin ≥ 10 g/dl.
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Canada | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT02780024 | ||||||||
Other Study ID Numbers ICMJE | MUHC ID: 4315 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product | Not Provided | ||||||||
IPD Sharing Statement ICMJE |
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Responsible Party | George Shenouda, McGill University Health Centre/Research Institute of the McGill University Health Centre | ||||||||
Study Sponsor ICMJE | McGill University Health Centre/Research Institute of the McGill University Health Centre | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | McGill University Health Centre/Research Institute of the McGill University Health Centre | ||||||||
Verification Date | November 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |