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後頭蓋窩グループA（PFA）上衣腫患者におけるメトホルミンの標的検証と有効性 (PNOC041)

2026年11月5日 更新者：University of California, San Francisco

再発または進行性後頭蓋窩群A（PFA）上衣腫患者におけるメトホルミンの標的検証および有効性研究

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.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

PRIMARY OBJECTIVES:

I. 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:

I. 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.

研究の種類

介入

入学 (推定)

30

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

  • 名前：PNOC Operations Office
  • 電話番号：415-502-1600
  • メール：PNOC041@ucsf.edu

研究場所

  • アメリカ
    • Alabama
      • Birmingham、Alabama、アメリカ、35233
        • 募集
        • University of Alabama at Birmingham
        • コンタクト：
        • コンタクト：
    • California
      • San Francisco、California、アメリカ、94143
        • 募集
        • University of California, San Francisco
        • 主任研究者：
          • Sabine Mueller, MD, PhD
        • コンタクト：
          • PNOC Operations Office
          • 電話番号：415-502-1600
          • メール：PNOC041@ucsf.edu
    • District of Columbia
      • Washington D.C.、District of Columbia、アメリカ、20010
        • 募集
        • Children's National Medical Center
        • コンタクト：
        • コンタクト：
    • Indiana
      • Indianapolis、Indiana、アメリカ、46202
        • まだ募集していません
        • Riley Hospital for Children at Indiana University Health
        • コンタクト：
          • Brian Weiss, MD
          • 電話番号：317-944-8784
          • メール：weissbd@iu.edu
        • コンタクト：
          • Alex Lion, DO, MPH
          • 電話番号：317-944-8784
          • メール：alion@iu.edu
    • Maryland
      • Baltimore、Maryland、アメリカ、21287
        • 募集
        • Johns Hopkins University
        • コンタクト：
          • Kenneth Cohen, MD, MBA
          • 電話番号：410-614-5055
          • メール：kcohen@jhmi.edu
        • コンタクト：
          • Robyn Gartrell, MD
          • 電話番号：410-614-5055
          • メール：rgartre1@jh.edu
    • Michigan
      • Ann Arbor、Michigan、アメリカ、48109
        • まだ募集していません
        • University of Michigan
        • コンタクト：
        • コンタクト：
    • Missouri
      • St Louis、Missouri、アメリカ、63110
        • 募集
        • Washington University
        • コンタクト：
        • コンタクト：
    • New Jersey
      • Hackensack、New Jersey、アメリカ、07601
        • まだ募集していません
        • Hackensack Meridian Health
        • コンタクト：
        • コンタクト：
    • North Carolina
      • Durham、North Carolina、アメリカ、27710
    • Tennessee
      • Memphis、Tennessee、アメリカ、38105
        • まだ募集していません
        • St. Jude Children's Research Hospital
        • コンタクト：
        • コンタクト：
    • Utah
      • Salt Lake City、Utah、アメリカ、84113
    • Washington
  • ブラジル
    • São Paulo
      • São Paulo、São Paulo、ブラジル、04039-001
        • まだ募集していません
        • GRAACC - Grupo de Apoio ao Adolescente e a Crianca com Cancer
        • コンタクト：
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

1年～39年 (子、大人)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  1. Participants must have recurrent or progressive posterior fossa A (PFA) ependymoma following surgery AND radiation treatment (RT).

  2. Participants must have a diagnosis of PFA ependymoma. Any number of previous recurrences are permissible provided the participant meets other enrollment criteria.

  3. 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 as outlined above.

  4. 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.

  5. Age: 1 -39 years at the time of enrollment.

  6. 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.

  7. Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.

  8. Organ Function Requirements

    1. Peripheral absolute neutrophil count (ANC) >= 1000/mm^3.
    2. Platelet count >=100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
    3. Serum creatinine < 1.5 Upper Limit normal (ULN) based on age and gender
    4. 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
    5. alanine aminotransferase (ALT) <= 3 x ULN.
    6. aspartate aminotransferase (AST) <=3 x ULN.

  9. 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.

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

  11. 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:

  1. 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).
  2. Participants without any measurable disease.
  3. 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.
  4. 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.
  5. 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
  6. Participants who are receiving any other investigational agents.
  7. Concurrent radiation therapy in any form is not permitted while on the study drug
  8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin.
  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
  10. Women of childbearing potential must not be pregnant or breast-feeding.
  11. 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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：非ランダム化
  • 介入モデル：順次割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：Target Validation (TV) Phase (Metformin)

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).
手順：Magnetic Resonance Imaging (MRI)

Undergo MRI imaging

他の名前：
  • MRI
薬：Metformin

Given orally (PO)

他の名前：
  • グルコファージ
手順：Planned Surgical Resection

Undergo planned surgery as part of regular care

他の名前：
  • 外科的切除
手順：Specimen Collection

Tumor Tissue, blood, and cerebral spinal fluid (CSF) may be collected for correlative analysis.

他の名前：
  • 試料サンプル収集
手順：MR spectroscopy (MRS)

Undergo MRS imaging

他の名前：
  • 夫人
実験的：Efficacy Phase (Metformin)

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).
手順：Magnetic Resonance Imaging (MRI)

Undergo MRI imaging

他の名前：
  • MRI
薬：Metformin

Given orally (PO)

他の名前：
  • グルコファージ
手順：Planned Surgical Resection

Undergo planned surgery as part of regular care

他の名前：
  • 外科的切除
手順：Specimen Collection

Tumor Tissue, blood, and cerebral spinal fluid (CSF) may be collected for correlative analysis.

他の名前：
  • 試料サンプル収集
手順：MR spectroscopy (MRS)

Undergo MRS imaging

他の名前：
  • 夫人

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Proportion of participants with changes in biomarkers between the pre-and post-metformin treated samples (Target Validation Phase)
時間枠：From initiation of study treatment until surgical resection of tumor, approximated 6 weeks

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)
時間枠：From initiation of study treatment until discontinuation of treatment, up to 2 years

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University of California, San Francisco

協力者

Pediatric Neuro-Oncology Consortium
The Lilabean Foundation, Inc.

捜査官

  • 主任研究者：Sabine Mueller, MD, PhD、University of California, San Francisco
  • スタディチェア：Santhosh A Upadhyaya, MD、University of Michigan, C. S. Mott Children's Hospital

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年5月5日

一次修了 (推定)

2028年4月30日

研究の完了 (推定)

2030年3月31日

試験登録日

最初に提出

2025年11月6日

QC基準を満たした最初の提出物

2025年11月6日

最初の投稿 (実際)

2025年11月10日

学習記録の更新

投稿された最後の更新 (実際)

2026年11月9日

QC基準を満たした最後の更新が送信されました

2026年11月5日

最終確認日

2026年11月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

  • 25087
  • NCI-2025-08332 (レジストリ識別子：NCI Clinical Trials Reporting Program (CTRP))

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

De-identified datasets may be shared with research collaborators during the course of the study.

IPD 共有サポート情報タイプ

  • STUDY_PROTOCOL
  • SAP
  • ICF

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

はい

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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