Metformin for Brain Tumor

(PNOC041 Trial)

Overseen By Denise Truong

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Metformin, Investigational agents

Disqualifiers: Diabetes, Rapid progression, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of metformin in treating a type of brain tumor called Posterior Fossa Group A (PFA) ependymoma in children and young adults. Researchers aim to determine if metformin can slow or stop the growth of tumors that have returned or worsened after previous treatments. Participants who have undergone surgery and radiation for PFA ependymoma but still experience recurring or progressing tumors may be suitable for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on metformin or any investigational agents. If you're on dexamethasone or anti-seizure medication, you must be on a stable dose for at least a week before joining.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research has shown that metformin is usually well-tolerated. In a small study with 24 children and teens who underwent brain radiation treatment, metformin proved to be safe and manageable. Another study confirmed its safety for children who survived brain tumors. Additionally, the FDA has approved metformin for treating diabetes, further supporting its safety. However, like any treatment, it may cause side effects, so discussing these with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain tumors?

Metformin is unique because it offers a potential new approach to treating brain tumors, specifically PFA ependymoma, by using a drug traditionally prescribed for diabetes. Unlike standard treatments like surgery and radiation, metformin is taken orally, which could make it a more convenient option for patients. Researchers are excited about metformin because it might work by influencing cancer cell metabolism, potentially slowing down tumor growth in a way that's different from existing therapies. This could offer new hope for patients whose tumors have not responded to traditional methods.

What evidence suggests that metformin might be an effective treatment for brain tumors?

Research has shown that metformin might help treat brain tumors by slowing their growth. In studies with aggressive brain tumors, metformin was linked to longer survival and slower tumor progression. It also appears to make tumor cells more responsive to treatments like chemotherapy and radiation. Metformin might target specific cancer cells that can cause tumors to recur, potentially preventing this. These early findings suggest that metformin could be effective for brain tumors like PFA ependymoma. Participants in this trial will receive metformin in either the Target Validation Phase or the Efficacy Phase, depending on their disease status and treatment history. ^{1 2 3 4 6}

Who Is on the Research Team?

Sabine Mueller, MD, PhD

Principal Investigator

University of California, San Francisco

Santhosh A Upadhyaya, MD

Principal Investigator

University of Michigan, C. S. Mott Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1-39 with recurrent or progressive PFA ependymoma, a type of brain tumor. They must have had prior surgery and radiation, controlled seizures if present, no diabetes or pre-diabetes, not pregnant or breastfeeding, and meet specific organ function criteria. Participants cannot be on metformin already or have uncontrolled illnesses.

Inclusion Criteria

Participant must have measurable disease defined as lesions that can be accurately measured in two dimensions

Participants must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution

A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate

Exclusion Criteria

Participants who are receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin

I have diabetes or my blood test shows I'm at risk for diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Target Validation (TV) Phase

Participants receive daily oral metformin with a weekly increasing dosage schedule prior to planned surgery

6 weeks

Weekly visits for dosage adjustment

Efficacy Phase

Participants receive daily oral metformin until disease progression or unacceptable adverse events

Up to 2 years

Regular MRI assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment under the PNOC COMP protocol

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests the effects of Metformin on PFA ependymoma in patients who are undergoing surgical resection. It includes MRI and MRS imaging techniques along with specimen collection to assess the drug's impact on the tumor.

How Is the Trial Designed?

Group I: Target Validation (TV) Phase (Metformin) Experimental Treatment 5 Interventions

Participants will each receive daily oral metformin with a weekly schedule starting at 250 mg/m\^2 twice a day (BID) for the first week, then increasing to 500 mg/m\^2 BID for week 2, 1000 mg/m\^2 BID for week 3, and then 1666 mg/m\^2 BID for week 4-6 prior to planned surgery. Participants with no measurable disease following surgical intervention may either go off treatment or continue metformin at the physician's discretion. Participants have the option of continuing on the efficacy phase of the study without undergoing planned surgery no demonstrated progressive disease on pre-surgery MRI AND if the family opts to continue treatment with metformin without undergoing surgical resection of the tumor. Participants with measurable tumor by RAPNO criteria following surgery may continue onto efficacy phase and receive maintenance metformin until disease progression or till there are unacceptable adverse event(s).

Group II: Efficacy Phase (Metformin) Experimental Treatment 5 Interventions

Participants with recurrent or progressive PFA ependymoma that have failed upfront surgery and radiation will receive daily oral metformin until disease progression or till there are unacceptable adverse event(s). Disease response will be assessed by MRI imaging using RAPNO criteria. Participants already enrolled on the TV phase may enroll in this phase if they have measurable disease post-surgery. Treatment may continue until disease progression or until there are unacceptable adverse event(s).

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

The Lilabean Foundation, Inc.

Collaborator

Pediatric Neuro-Oncology Consortium

Collaborator

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7016983/

Metformin as Potential Therapy for High-Grade Glioma - PMC The use of metformin has been associated with better overall and progression-free survival of patients with high-grade glioma [9]. Repurposing metformin as ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1936523325000543

Metformin and glioma: Targeting metabolic dysregulation ... Preclinical studies demonstrate metformin's efficacy in reducing tumor growth and enhancing the sensitivity of glioma cells to chemotherapy and radiotherapy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05230758

Study Details | NCT05230758 | Effect of Metformin on ... We hypothesize that 16 weeks of treatment with metformin will be associated with better cognitive outcomes than 16 weeks of treatment with placebo.

4. mdpi.com mdpi.com/1422-0067/25/11/5694

Advances in Anti-Cancer Drug Development: Metformin as ... By targeting glioma stem cells, metformin may reduce tumor recurrence and enhance the overall effectiveness of TMZ and radiation therapy. Metformin can increase ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2051

Phase I/II study of maintenance therapy with metformin and ... Our phase I findings indicated that MF at doses of up to 2,250 mg/day combined with maintenance TMZ was well tolerated (Cancers, 2022). Here, we ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8176964/

Assessment of cognitive and neural recovery in survivors of ... Second, for our primary endpoint in the pilot trial, we found that metformin is safe to use and tolerable in survivors of pediatric brain tumors. While an ...