Glioblastoma, IDH-wildtypePhase 2NCT05929495
Phase 2, Open-label, Single-arm Study on the Use of Metformin as Adjunctive Therapy in High-grade Glioma
A Phase 2 study testing Metformin in people with Glioblastoma, IDH-wildtype and Metformin, run by University of Milano Bicocca at 1 site in Italy.
Trial summary
About 75% of CNS malignant tumors are classified as gliomas and the IDH-wildtype glioblastoma (GBM) represents the most aggressive form among CNS malignancies. This is a nationwide single-center phase II drug clinical trial with an approximate duration of 32 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, IDH-wildtype, Metformin, Malignancies
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- 12 Feb 2024to 1 Jan 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with newly diagnosed histologically confirmed GBM (WHO grade IV, IDH wild type) undergoing surgical resection;
- hypomethylation or hypermethylation of MGMT assessed post-surgery;
- adult patients (≥18 years), both sexes;
- Patients undergoing Stupp protocol including patients aged > 70 years performing the hypofractionated protocol and three weeks of chemotherapy;
- Karnofsky Performance Status (KPS)> 60 assessed post-surgery;
- life expectancy at least 6 months defined by size and location of lesion tumor;
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- freely given written informed consent prior to any activity related to the study. Patients must be able to communicate with the investigator and comply with the study procedures;
- Women of childbearing age must test negative for pregnancy at enrollment and, if they have sexual intercourse, they must agree to use specific contraceptive methods. Female subjects of childbearing age, i.e., fertile, after menarche and until post-menopause unless they are permanently infertile, who are sexually active, must apply a highly effective method of birth control with a low failure rate (i.e., less than 1 percent per year), such as combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral intravaginal, or transdermal), progestin-only hormonal contraception associated with ovulation inhibition (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone delivery system (IUS), bilateral tubal occlusion, vasectomized partner, or sexual abstinence, throughout the treatment period and for four weeks after the last dose of the study treatment. Hormonal methods other than levonorgestrel-containing devices or medroxyprogesterone injections should be supplemented with the use of a male condom. Women of nonfertile age may be included if surgically sterile or postmenopausal for at least 2 years. The investigator is responsible for determining whether the patient has adopted an appropriate method of contraception for participation in the study.
- Male subjects with female partners of childbearing age must use condoms during treatment and until the end of relevant systemic exposure.
Who cannot join
- Multicenter GBMs;
- Patients diagnosed with diabetes or diabetes-related conditions;
- other active malignancies;
- hypersensitivity, intolerance to metformin or excipients;
- Impaired renal function with creatinine clearance < 60 mL/min assessed at recruitment, liver failure assessed at recruitment by clinical history and examination of ALT, AST and total bilirubin, and other contraindications to metformin use;
- taking metformin, insulin or other biguanides, regardless of the reason;
- pregnancy or lactation;
- patient has serious pre-existing medical conditions that, in the opinion of the investigator, would preclude participation in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
Milan
Manuela Caroli, MD, 0255035502, manuela.caroli@policlinico.mi.it
About this study
About 75% of CNS malignant tumors are classified as gliomas and the IDH-wildtype glioblastoma (GBM) represents the most aggressive form among CNS malignancies.
This is a nationwide single-center phase II drug clinical trial with an approximate duration of 32 months.
The clinical trial will be single-arm to evaluate the biological activity and effects of metformin in combination with TMZ in patients with GBM.
Read the detailed description
About 75% of CNS malignant tumors are classified as gliomas, tumors of neuroectodermal origin arising from glial cells or glial cell precursors. The World Health Organization classification distinguishes gliomas into low-grade gliomas (low-grade gliomas, grade I and II) and high-grade gliomas (high-grade gliomas, grade III and IV).
IDH-wildtype glioblastoma (GBM) represents the most aggressive form among CNS malignancies.
Over the past century, numerous epidemiological and experimental observations have reported a preventive and beneficial antitumor effect of metformin, which has suggested the possibility of using it as adjunctive therapy in many cancer subtypes, including GBM.
The aim of this study is to evaluate the effect of Metformin as adjuvant therapy to TMZ in the treatment of patients with GBM.
Patients will start with a Metformin dose of 1 g/day orally in two administrations (500 mg tablets) during the first two weeks of treatment, increasing to 2 g/day in two 1 g tablets thereafter.
The approximate total duration of the study is 32 months, and 25 patients will be enrolled
- Conditions
- Glioblastoma, IDH-wildtype, Metformin, Malignancies
- Being tested
- Metformin
- Keywords
- Metformin, Gliomas, GBM
- Medical subject headings
- Glioblastoma, Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
The investigator will identify potential participants and confirm the diagnosis of GBM. Subjects will be screened within 6 weeks before starting treatment.
Treatment will involve:
- Administration of the standard or partial Stupp protocol (Radiotherapy + Temozolomide) in combination with Metformin for 6 weeks,
- Treatment with only Metformin for 4 weeks;
- Resumption of adjuvant TMZ + Metformin treatment continuously until the end of the enrollment period.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | 25 patients with GBM will take 1g/day of Metformin (2 tablets of 500 mg) for two weeks and then take 2g/day of Metformin for a total of 6 weeks. At the end of 6 weeks, treatment with Metformin alone will be continued for 4 weeks.
Thereafter, the second-phase Stupp protocol (adjuvant TMZ) + metformin is resumed continuously until the end of the enrollment period, i.e., 58 weeks from the start of treatment, for each patient. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Value of PFS at 6 months after the start of treatment
It allow us to determine the efficacy at the recommended dose (RD) of metformin in patients with GBM
Measured: Frome baseline to 6 months
Secondary outcomes (8)
EORTC QLQ-C30 questionnaire at 6 months after the start of treatment
The Quality of Life of Cancer Patients questionnaire allow us to evaluate the change in the level of health-related quality of life.
It consists of several questions that the patient must answer by choosing a value from 1 (minimum) to 4/7 (maximum), depending on the question.
Measured: Frome baseline to 6 months
MMSE questionnaire at 6 months after the start of treatment
The Mini Mental State Evaluation questionnaire allow us to evaluate the change in the level of health-related quality of life.
It consists of several questions for the patient to answer, but there are no minimum or maximum values for the patient to choose from.
Measured: Frome baseline to 6 months
Safety and tolerability assessment of treatment
Safety will be assessed throughout the study as type, frequency and severity of grade III and IV events.
Tolerability will be assessed as number of discontinuations or dose reduction and by evaluation of clinical and hematochemical parameters
Measured: From baseline through study completion, an average of 32 months
Plasma measurement of circulating metabolites
Peri-operative plasma will be taken from each patient for hematochemical analysis, in order to research of prognostic biomarkers.
Measured: At study completion, an average of 32 months
Plasma measurement of adiponectin
Peri-operative plasma will be taken from each patient for hematochemical analysis, in order to research of prognostic biomarkers.
Measured: At study completion, an average of 32 months
Proteomic analysis
Peri-operative plasma will be taken from each patient for proteomic analysis, in order to research of prognostic biomarkers.
Measured: At study completion, an average of 32 months
Correlations between in vivo clinical response and effect of association measured in vitro on cell lines obtained from the same patient undergoing surgery
In vitro cell response measured as cell growth inhibition and correlation with clinical response (PFS) of the same patient.
Measured: At the end of recruitment, an average of 18 months
Gene expression analysis
Identifying the molecular phenotype of cells taken from patients' tissue samples during surgery and comparing clinical response and molecular phenotype by transcriptomic analysis
Measured: At the end of recruitment, an average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2023
- Study start12 Feb 2024
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma, IDH-wildtypeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Metformin dose of 1 g/day orally in two administrations (500 mg tablets) during the first two weeks of treatment, increasing to 2 g/day in two 1 g tablets thereafter
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milano Bicocca
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05929495
- Sponsor's protocol ID
- GBM MET
- Status last verified
- Jul 2025
- First submitted
- 13 Jun 2023
- Last updated
- 25 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Open-label, Single-arm Study on the Use of Metformin as Adjunctive Therapy in High-grade Glioma
- ClinicalTrials.gov ID
- NCT05929495
- Acronym / sponsor ID
- GBM MET
- Conditions
- Glioblastoma, IDH-wildtype, Metformin, Malignancies
- Keywords
- Metformin, Gliomas, GBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of Milano BicoccaUniversity, hospital or other
- Study start
- 12 Feb 2024 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 3 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
About 75% of CNS malignant tumors are classified as gliomas and the IDH-wildtype glioblastoma (GBM) represents the most aggressive form among CNS malignancies.
This is a nationwide single-center phase II drug clinical trial with an approximate duration of 32 months.
The clinical trial will be single-arm to evaluate the biological activity and effects of metformin in combination with TMZ in patients with GBM.
Detailed description
About 75% of CNS malignant tumors are classified as gliomas, tumors of neuroectodermal origin arising from glial cells or glial cell precursors. The World Health Organization classification distinguishes gliomas into low-grade gliomas (low-grade gliomas, grade I and II) and high-grade gliomas (high-grade gliomas, grade III and IV).
IDH-wildtype glioblastoma (GBM) represents the most aggressive form among CNS malignancies.
Over the past century, numerous epidemiological and experimental observations have reported a preventive and beneficial antitumor effect of metformin, which has suggested the possibility of using it as adjunctive therapy in many cancer subtypes, including GBM.
The aim of this study is to evaluate the effect of Metformin as adjuvant therapy to TMZ in the treatment of patients with GBM.
Patients will start with a Metformin dose of 1 g/day orally in two administrations (500 mg tablets) during the first two weeks of treatment, increasing to 2 g/day in two 1 g tablets thereafter.
The approximate total duration of the study is 32 months, and 25 patients will be enrolled
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Metformin dose of 1 g/day orally in two administrations (500 mg tablets) during the first two weeks of treatment, increasing to 2 g/day in two 1 g tablets thereafter
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin25 patients with GBM will take 1g/day of Metformin (2 tablets of 500 mg) for two weeks and then take 2g/day of Metformin for a total of 6 weeks. At the end of 6 weeks, treatment with Metformin alone will be continued for 4 weeks. Thereafter, the second-phase Stupp protocol (adjuvant TMZ) + metformin is resumed continuously until the end of the enrollment period, i.e., 58 weeks from the start of treatment, for each patient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with newly diagnosed histologically confirmed GBM (WHO grade IV, IDH wild type) undergoing surgical resection;
- hypomethylation or hypermethylation of MGMT assessed post-surgery;
- adult patients (≥18 years), both sexes;
- Patients undergoing Stupp protocol including patients aged > 70 years performing the hypofractionated protocol and three weeks of chemotherapy;
- Karnofsky Performance Status (KPS)> 60 assessed post-surgery;
Key exclusion criteria (8 listed)
- Multicenter GBMs;
- Patients diagnosed with diabetes or diabetes-related conditions;
- other active malignancies;
- hypersensitivity, intolerance to metformin or excipients;
- Impaired renal function with creatinine clearance < 60 mL/min assessed at recruitment, liver failure assessed at recruitment by clinical history and examination of ALT, AST and total bilirubin, and other contraindications to metformin use;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminThe investigator will identify potential participants and confirm the diagnosis of GBM. Subjects will be screened within 6 weeks before starting treatment. Treatment will involve: * Administration of the standard or partial Stupp protocol (Radiotherapy + Temozolomide) in combination with Metformin for 6 weeks, * Treatment with only Metformin for 4 weeks; * Resumption of adjuvant TMZ + Metformin treatment continuously until the end of the enrollment period. | Drug | Metformin |
Primary outcome
Value of PFS at 6 months after the start of treatment
Time frame: Frome baseline to 6 months
It allow us to determine the efficacy at the recommended dose (RD) of metformin in patients with GBM
8 secondary outcomes
EORTC QLQ-C30 questionnaire at 6 months after the start of treatment
Time frame: Frome baseline to 6 months
MMSE questionnaire at 6 months after the start of treatment
Time frame: Frome baseline to 6 months
Safety and tolerability assessment of treatment
Time frame: From baseline through study completion, an average of 32 months
Plasma measurement of circulating metabolites
Time frame: At study completion, an average of 32 months
Plasma measurement of adiponectin
Time frame: At study completion, an average of 32 months
Proteomic analysis
Time frame: At study completion, an average of 32 months
Correlations between in vivo clinical response and effect of association measured in vitro on cell lines obtained from the same patient undergoing surgery
Time frame: At the end of recruitment, an average of 18 months
Gene expression analysis
Time frame: At the end of recruitment, an average of 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Glioblastoma, IDH-wildtype and Metformin, run by University of Milano Bicocca at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manuela Caroli, Dott.ssa (0255035502, manuela.caroli@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Value of PFS at 6 months after the start of treatment (time frame: Frome baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025.