Clinical trial on the use of metformin in addition to standard therapy in patients with high-grade glioma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita Degli Studi Di Milano Bicocca

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Feb 2025 → ongoing

Decision date (initial)

2025-02-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fondazione AIRC per la Ricerca sul Cancro

External identifiers

EU CT number

2024-520228-28-00

EudraCT number

2022-003595-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Determine efficacy at the recommended dose of metformin in patients with glioblastoma. Efficacy will be assessed by PFS at 6 months after initiation of treatment. Radiographic response will be assessed by RANO (Response Assessment in Neurooncology) criteria compared with the patient's condition at baseline (MRI performed postsurgery)

Secondary objectives 1

1. 1) Assessment of change in health-related quality of life (EORTC QLQ-C30 and MMSE) at 6 months after the start of treatment. 2) Evaluation safety and tolerability of treatment measured as frequency and severity of adverse events throughout the study. The data obtained will be compared with historical data. 3) Search for clinical and plasma prognostic biomarkers. 4) Exploration of possible correlations between in vivo clinical response and effect of association measured in vitro on cell lines obtained from the same patient undergoing surgery.

Conditions and MedDRA coding

IDH-wildtype glioblastoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. - Patients with newly diagnosed histologically confirmed GBM (WHO grade IV, IDH wild type) undergoing surgical resection;
2. - Hypomethylation or hypermethylation of MGMT evaluated post-surgery;
3. - Adult patients (=18 years), both sexes;
4. - Patients undergoing Stupp protocol including patients aged >70 years performing hypofractionated protocol and three weeks of chemotherapy;
5. - Karnofsky Performance Status (KPS) > 60 assessed post-surgery;
6. - Life expectancy at least 6 months defined by tumor lesion size and location;
7. - Freely given written informed consent prior to any study-related activity. Patients must be able to communicate with the investigator and comply with study procedures;
8. - Women of childbearing age must test negative for pregnancy at enrollment and, if they have sex, must agree to use specific contraceptive methods. Female subjects of childbearing age, i.e., fertile, after menarche and until post-menopause unless 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.
9. - Male subjects with female partners of childbearing age must use condoms during treatment and until the end of relevant systemic exposure.

Exclusion criteria 8

1. - Multicenter GBMs;
2. - Patients diagnosed with diabetes or diabetes-related conditions;
3. - Other active malignancies;
4. - Hypersensitivity, intolerance to metformin or excipients;
5. - 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;
6. - Taking metformin, insulin or other biguanides, regardless of the reason;
7. - Pregnancy or lactation;
8. - The patient has serious pre-existing medical conditions that, in the opinion of the investigator, would preclude participation in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS assessed at V3 (at approximately 6 months after treatment initiation). Progression is defined as recurrence from documentable disease on MRI by assessment with RANO (Response Assessment in Neurooncology) criteria (MRI T1w-Gd; T2 Flair)

Secondary endpoints 4

1. Health-related quality of life measured by EORTC QLQ-C30 and MMSE questionnaires assessed at V0 and V3. The data obtained will be compared with population data
2. 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 (blood count, liver and kidney toxicity, blood glucose) assessed during the study.
3. Plasma measurement of circulating metabolites, adiponectin and proteomic analysis as potential prognostic and response markers. Overall assessment of this endpoint will be performed at the end of the study.
4. In vitro response of cells taken from patients' tissue samples during surgery to treatment with TMZ or TMZ plus MET or vehicle measured as cell growth inhibition and correlation with clinical response (PFS) of the same patient. - Transcriptomic analysis to identify the molecular phenotype of cells taken from patients' tissue samples during surgery and comparison between clinical response and molecular phenotype. Evaluation of these endpoints will be performed at the end of recruitment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita Degli Studi Di Milano Bicocca

Sponsor organisation

Universita Degli Studi Di Milano Bicocca

Address

Piazza Dell'ateneo Nuovo 1

City

Milan

Postcode

20126

Country

Italy

Scientific contact point

Organisation

Universita Degli Studi Di Milano Bicocca

Contact name

Rosa Moresco

Public contact point

Organisation

Universita Degli Studi Di Milano Bicocca

Contact name

Rosa Moresco

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications