Posterior Fossa Ependymal TumorPhase 2PNOC041NCT07226453

Target Validation and Efficacy of Metformin in Patients With Posterior Fossa Group A (PFA) Ependymoma

A Phase 2 study testing Metformin, Planned Surgical Resection and Magnetic Resonance Imaging (MRI) in people with Posterior Fossa Ependymal Tumor, run by University of California, San Francisco at 12 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

This is a multi-site study of the pharmacodynamic effects and efficacy of metformin in children and young adults with recurrent or progressive Posterior Fossa Group A (PFA) ependymoma. Read more about this study

Who is it for?: Ages 1 year to 39 years
Conditions the study is for: Posterior Fossa Ependymal Tumor
What is being tested?: Metformin, Planned Surgical Resection and Magnetic Resonance Imaging (MRI)
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 12 sitesUnited States
Study dates: 5 May 2026to 31 Mar 2030
Phase: Phase 2

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 1 year to 39 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Participants must have recurrent or progressive posterior fossa A (PFA) ependymoma following surgery AND radiation treatment (RT).
Participants must have a diagnosis of PFA ependymoma. Any number of previous recurrences are permissible provided the participant meets other enrollment criteria.
Participants must have adequate tumor tissue available from initial diagnosis or from pre- trial enrollment. Formalin-fixed paraffin-embedded (FFPE) material (1 full block) should be provided. If FFPE material is not available, 10 unstained slides with an accompanying hematoxylin and eosin (H\&E) report should be provided.
Target Validation (TV) Phase:
o Participants are candidates to undergo elective surgery for removal of all or a portion of their recurrent/progressive tumor.
Efficacy Phase:

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Participant must have measurable disease; this will be defined as lesions that can be accurately measured in two dimensions (longest diameter to be recorded) The size threshold is met if both in-plane diameters are ≥10 mm or both in-plane diameters are at least two times the MRI slice thickness, plus the interslice gap with a minimum size of no less than double the slice thickness on MRI.
Participants with an isolated local progression of the tumor following RT (or stereotactic radiosurgery, SRS) must be > 6 months from completion of RT to the lesion to rule out pseudo progression or must have tissue confirmation of progression prior to enrollment.
Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy as outlined above.
Prior Therapy: Participants must not be receiving metformin for other medical indications or previous exposure to metformin following their diagnosis of PFA ependymoma. However, participants treated on the TV phase, but did not continue onto maintenance therapy will be allowed to enroll on the efficacy phase with future recurrences or progression of their disease.
Age: 1 -39 years at the time of enrollment.
Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >=50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
Organ Function Requirements
Peripheral absolute neutrophil count (ANC) >= 1000/mm^3.
Platelet count >=100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
Serum creatinine < 1.5 Upper Limit normal (ULN) based on age and gender
Total bilirubin <= 1.5 x ULN for age; in presence of Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN
alanine aminotransferase (ALT) <= 3 x ULN.
aspartate aminotransferase (AST) <=3 x ULN.
Participants with seizure disorder may be enrolled if well controlled and are on stable dose of anti-seizure medication for > 72 hours prior to enrollment. Participants who have neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
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.

Who cannot join

Participants with a history of diabetes mellitus or those meeting criteria for pre-diabetes are excluded. Pre-diabetes is defined per American Diabetes Association criteria as any of the following: fasting plasma glucose (FPG) 100-125 mg/dL (5.6-6.9 mmol/L); 2-hour plasma glucose (OGTT) 140-199 mg/dL (7.8-11.0 mmol/L); or hemoglobin A1c (HbA1c) 5.7%-6.4% (39-47 mmol/mol).
Participants without any measurable disease.
Participants who have had chemotherapy or have received radiotherapy to the non-target lesion within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
Participants with rapidly progressive symptoms that require urgent surgery that in the investigators assessment cannot be safely deferred for 6 weeks are excluded from target validation phase of the study
Participants who are receiving any other investigational agents.

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Concurrent radiation therapy in any form is not permitted while on the study drug
History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
Women of childbearing potential must not be pregnant or breast-feeding.
Human immunodeficiency virus- (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised.

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

PNOC Operations Office contact

415-502-1600

PNOC041@ucsf.edu

City, postcode or hospital

Sites recruiting now only

12 sites in 1 country

United States12 sites, 12 recruiting

University of Michigan
Ann Arbor, Michigan, 48109
Andrea Franson, MD, MS, 734-232-9335, atflynn@med.umich.edu
Carl Koschmann, MD, 734-232-9355, ckoschma@med.umich.edu
Not yet recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Kenneth Cohen, MD, MBA, 410-614-5055, kcohen@jhmi.edu
Robyn Gartrell, MD, 410-614-5055, rgartre1@jh.edu
Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Girish Dhall, MD, 205-638-9285, gdhall@peds.uab.edu
Katie Metrock, MD, 205-638-9285, kmetrock@uabmc.edu
Recruiting
Duke University
Durham, North Carolina, 27710
Daniel Landi, MD, 919-684-5580, daniel.landi@duke.edu
Kristin Schroeder, MD, 919-684-5580, kristin.schroeder@duke.edu
Recruiting
Hackensack Meridian Health
Hackensack, New Jersey, 07601
Derek Hanson, MD, 551-996-5437, Derek.Hanson@HMHN.org
Katharine Offer, MD, 551-996-5437, Katharine.Offer@HMHN.org
Not yet recruiting
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
Brian Weiss, MD, 317-944-8784, weissbd@iu.edu
Alex Lion, DO, MPH, 317-944-8784, alion@iu.edu
Not yet recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Amar Gajjar, MD, 901-595-2615, amar.gajjar@stjude.org
Christopher Tinkle, MD, 901-595-2615, christopher.tinkle@stjude.org
Not yet recruiting
University of Utah
Salt Lake City, Utah, 84113
Nicholas Whipple, MD, MPH, 801-662-4700, nicholas.whipple@hsc.utah.edu
Priya Chan, MD, 801-662-4700, priya.chan@hsc.utah.edu
Recruiting
University of California, San Francisco
San Francisco, California, 94143
PNOC Operations Office, 415-502-1600, PNOC041@ucsf.edu
Sabine Mueller, MD, PhD
Recruiting
Seattle Children's
Seattle, Washington, 98101
Erin Crotty, MD, 206-987-2106, erin.crotty@seattlechildrens.org
Daniel Runco, MD, 206-987-2106, daniel.runco@seattlechildrens.org
Recruiting
Washington University
St Louis, Missouri, 63110
Michael A Huang, MD, 314-286-2790, muhuang@wustl.edu
Mohamed S Abdelbaki, MD, 314-286-2790, mohameda@wustl.edu
Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Lindsay Kilburn, MD, 202-476-5973, lkilburn@cnmc.org
Adriana Fonseca, MD, 202-476-5973, afonsecash@childrensnational.org
Recruiting

Other trials in United States

About this study

Official title: A Target Validation and Efficacy Study of Metformin in Patients With Recurrent or Progressive Posterior Fossa Group A (PFA) Ependymoma

This is a multi-site study of the pharmacodynamic effects and efficacy of metformin in children and young adults with recurrent or progressive Posterior Fossa Group A (PFA) ependymoma.

Read the detailed description

PRIMARY OBJECTIVES:

To assess pharmacodynamic effect on PFA tumor cells of metformin in participants with recurrent or progressive PFA undergoing surgical resection of the tumor by determining change in H3K27me3 and/or EZHIP expression in tumor nuclei compared to pre-treatment levels (TV Phase)

II. To measure disease stabilization rate by Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria (complete (CR), partial (PR) response; ≥50% reduction in size but <CR), and Stable (SD); < 50% reduction in size but not meeting criteria for progressive disease) in participants with recurrent or progressive PFA ependymoma following metformin treatment (Efficacy Phase).

EXPLORATORY OBJECTIVES:

Estimate the 1-year progression-free survival and overall-survival of participants with recurrent or progressive PFA treated with single agent metformin (Efficacy Phase).

II. To assess pharmacokinetics (PK) of metformin by measuring plasma, CSF and intra-tumoral concentration of metformin, the latter two obtained at the time of surgery or at the time of further disease progression on study in consenting participants (Both cohorts).

III. Evaluate the feasibility of using MR spectroscopy (MRS) imaging to study oncometabolite profile of recurrent or progressive PFA ependymoma pre-and post-treatment with metformin.

OUTLINE:

This will be a two-part study: a TV phase and an efficacy phase. Participants will be initially enrolled in the TV phase and receive treatment prior to planned surgery. Participants already enrolled on the TV phase may continue to the efficacy phase of the study if they have measurable disease post-surgery. Participants in the efficacy phase will receive daily oral metformin until disease progression or till there are unacceptable adverse event(s). Long term/survival follow-up procedures are to be captured under the Pediatric Neuro-Oncology Consortium (PNOC) Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies protocol (COMP). Participants will be followed under the PNOC COMP protocol until death or withdrawal from study.

Conditions: Posterior Fossa Ependymal Tumor
Being tested: Metformin, Planned Surgical Resection, Magnetic Resonance Imaging (MRI), Specimen Collection, MR spectroscopy (MRS)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MetforminDrug
Also called Glucophage
Given orally (PO)
Planned Surgical ResectionProcedure or surgery
Also called Surgical Resection
Undergo planned surgery as part of regular care
Magnetic Resonance Imaging (MRI)Procedure or surgery
Also called MRI
Undergo MRI imaging
Specimen CollectionProcedure or surgery
Also called Specimen Sample Collection
Tumor Tissue, blood, and cerebral spinal fluid (CSF) may be collected for correlative analysis.
MR spectroscopy (MRS)Procedure or surgery
Also called MRS
Undergo MRS imaging

Study groups in NCT07226453
Study group	Role	What they receive
Target Validation (TV) Phase (Metformin)	Experimental	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). Receives: Drug: Metformin; Procedure: Planned Surgical Resection; Procedure: Magnetic Resonance Imaging (MRI); Procedure: Specimen Collection; Procedure: MR spectroscopy (MRS)
Efficacy Phase (Metformin)	Experimental	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). Receives: Drug: Metformin; Procedure: Planned Surgical Resection; Procedure: Magnetic Resonance Imaging (MRI); Procedure: Specimen Collection; Procedure: MR spectroscopy (MRS)

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of participants with changes in biomarkers between the pre-and post-metformin treated samples (Target Validation Phase)
Proportion of participants with a 10% reduction in Enhancer of Zeste Inhibitory Protein (EZHIP) and/or a 10% increase in the epigenetic modification to the DNA packaging protein histone H3, with tri-methylation of lysine 27 on histone H3 (H3K27me3) between the pre- and post-metformin treated samples by Immunohistochemistry (IHC).
Measured: From initiation of study treatment until surgical resection of tumor, approximated 6 weeks
Disease Stabilization Rate (Efficacy Phase)
The primary endpoint of the efficacy phase is the disease stabilization rate by RAPNO criteria (complete (CR), partial (PR); response >50% reduction in size < CR, and stable (SD) which is a < 50% reduction in size and not meeting the definition for progressive disease) tumor responses), CR+PR+SD.
Measured: From initiation of study treatment until discontinuation of treatment, up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 May 202631 Mar 2030

First posted10 Nov 2025
Study start5 May 2026
Primary completion30 Apr 2028 (estimated)
Study completion31 Mar 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Posterior Fossa Ependymal TumorStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
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: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07226453
Sponsor's protocol ID: 25087
Other IDs: NCI-2025-08332
Acronym: PNOC041
Status last verified: Oct 2026
First submitted: 6 Nov 2025
Last updated: 20 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified datasets may be shared with research collaborators during the course of the study.