Target Validation and Efficacy of Metformin in Patients With Posterior Fossa Group A (PFA) Ependymoma
PNOC041
A Target Validation and Efficacy Study of Metformin in Patients With Recurrent or Progressive Posterior Fossa Group A (PFA) Ependymoma
2 other identifiers
interventional
30
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 6, 2025
CompletedFirst Posted
Study publicly available on registry
November 10, 2025
CompletedStudy Start
First participant enrolled
June 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2028
Study Completion
Last participant's last visit for all outcomes
March 31, 2030
April 22, 2026
April 1, 2026
1.9 years
November 6, 2025
April 20, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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).
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.
From initiation of study treatment until discontinuation of treatment, up to 2 years
Study Arms (2)
Target Validation (TV) Phase (Metformin)
EXPERIMENTALParticipants 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).
Efficacy Phase (Metformin)
EXPERIMENTALParticipants 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).
Interventions
Tumor Tissue, blood, and cerebral spinal fluid (CSF) may be collected for correlative analysis.
Undergo MRS imaging
Given orally (PO)
Undergo planned surgery as part of regular care
Undergo MRI imaging
Eligibility Criteria
You may qualify if:
- 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 either at initial diagnosis or at recurrence. 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:
- 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.
- 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.
- +8 more criteria
You may not qualify if:
- Participants with a history of diabetes mellitus or those found to have pre-diabetes on HbA1C screening test are excluded from the study.
- Participants without any measurable disease but with only isolated leptomeningeal disease progression.
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Lilabean Foundation, Inc.collaborator
- University of California, San Franciscolead
- Pediatric Neuro-Oncology Consortiumcollaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sabine Mueller, MD, PhD
University of California, San Francisco
- STUDY CHAIR
Santhosh A Upadhyaya, MD
University of Michigan, C. S. Mott Children's Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 6, 2025
First Posted
November 10, 2025
Study Start (Estimated)
June 1, 2026
Primary Completion (Estimated)
April 30, 2028
Study Completion (Estimated)
March 31, 2030
Last Updated
April 22, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
De-identified datasets may be shared with research collaborators during the course of the study.