Phase 2, Open-label, Single-arm Study on the Use of Metformin as Adjunctive Therapy in High-grade Glioma

NCT05929495 | Recruiting Phase 2

• 1 other identifier: GBM MET
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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. The clinical trial will be single-arm to evaluate the biological activity and effects of metformin in combination with TMZ in patients with GBM.

Conditions

Glioblastoma, IDH-wildtype; Metformin; Malignancies

Keywords

Metformin; Gliomas; GBM

Outcome Measures

Primary Outcomes (1)

• 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

  Frome baseline to 6 months

Secondary Outcomes (8)

• EORTC QLQ-C30 questionnaire at 6 months after the start of treatment

  Frome baseline to 6 months

• MMSE questionnaire at 6 months after the start of treatment

  Frome baseline to 6 months

• Safety and tolerability assessment of treatment

  From baseline through study completion, an average of 32 months

• Plasma measurement of circulating metabolites

  At study completion, an average of 32 months

• Plasma measurement of adiponectin

  At study completion, an average of 32 months

Study Arms (1)

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.

Drug: Metformin

Interventions

Metformin DRUG

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.

Metformin

Eligibility Criteria

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

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Milano Bicocca: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, Italy

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Neoplasms; Glioma

Interventions

Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Manuela Caroli, Dott.ssa

CONTACT

0255035502; manuela.caroli@policlinico.mi.it

Rosa Maria Moresco, Dott.ssa

CONTACT

0264488256; rosa.moresco@unimib.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: July 3, 2023
• Study Start: February 12, 2024
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)