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Fimepinostat w leczeniu guzów mózgu u dzieci i młodzieży (PNOC016)

28 października 2026 zaktualizowane przez: Sabine Mueller, MD, PhD

Docelowe badanie walidacyjne fimepinostatu u dzieci i młodych dorosłych z nowo zdiagnozowanym rozlanym glejakiem mostka (DIPG), nawracającym rdzeniakiem lub nawracającym glejakiem wysokiego stopnia (HGG)

This trial studies how well fimepinostat works in treating patients with newly diagnosed diffuse intrinsic pontine glioma, or medulloblastoma, or high-grade glioma that have come back. Fimepinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

PRIMARY OBJECTIVES:

I. To confirm penetration of fimepinostat across the blood brain barrier (BBB) in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG), recurrent medulloblastoma, or recurrent high-grade glioma (HGG) by measuring concentration of fimepinostat and metabolite in primary tumor tissue.

EXPLORATORY OBJECTIVES:

I. To assess pharmacokinetics (PK) of fimepinostat in plasma and tumor tissue of children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG.

II. To assess pharmacodynamics (PD) of fimepinostat in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG as measured by phosphorylation and acetylation in tumor tissue.

III. To correlate acetylation and phosphorylation in tumor tissue with tissue and plasma PK levels.

IV. To assess the safety and tolerability of fimepinostat in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG.

V. To assess preliminary efficacy of fimepinostat given as monotherapy after surgery in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG, as based on progression-free survival (PFS) and objective response rate (ORR) as appropriate.

OUTLINE:

Patients receive fimepinostat orally (PO) once daily (QD) on days -2 to 0. Within 2 hours of receiving fimepinostat on day 0, patients undergo tumor resection.

MAINTENANCE PHASE: Patients receive fimepinostat by mouth, once daily for days 1-5 each week. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 12 months from the time treatment begins. Should patients continue to derive clinical benefit, and not experience excess toxicity or progression, patients can continue to receive drug for up to 24 months or longer pending discussion with study chairs and study sponsor.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 5 years.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

30

Faza

  • Wczesna faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Stany Zjednoczone
    • California
      • Los Angeles, California, Stany Zjednoczone, 90027
        • Children's Hospital Los Angeles (CHLA)
      • San Diego, California, Stany Zjednoczone, 92123
        • Rady Children's Hospital
      • San Francisco, California, Stany Zjednoczone, 94143
        • University of California, San Francisco
    • District of Columbia
      • Washington D.C., District of Columbia, Stany Zjednoczone, 20010
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, Stany Zjednoczone, 32611
        • University of Florida
    • Illinois
      • Chicago, Illinois, Stany Zjednoczone, 60611
        • Lurie Children's Hospital of Chicago
    • Maryland
      • Baltimore, Maryland, Stany Zjednoczone, 21231
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, Stany Zjednoczone, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, Stany Zjednoczone, 48109
        • University of Michigan Hospital
    • Minnesota
      • Minneapolis, Minnesota, Stany Zjednoczone, 55404
        • Children's Minnesota Research Institute
    • Missouri
      • St Louis, Missouri, Stany Zjednoczone, 63110
        • Washington University in St Louis
    • Ohio
      • Columbus, Ohio, Stany Zjednoczone, 43205
        • Nationwide Children's
    • Oregon
      • Portland, Oregon, Stany Zjednoczone, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stany Zjednoczone, 19146
        • Children's Hospital of Philadelphia (CHOP)
    • Tennessee
      • Memphis, Tennessee, Stany Zjednoczone, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, Stany Zjednoczone, 77030
        • Texas Children's Hospital
    • Utah
      • Salt Lake City, Utah, Stany Zjednoczone, 84113
        • University of Utah, Children's Primary
    • Washington
      • Seattle, Washington, Stany Zjednoczone, 98105
        • Seattle Children's Hospital
  • Szwajcaria
    • Canton of Zurich
      • Zurich, Canton of Zurich, Szwajcaria, 8032
        • The University Children's Hospital in Zurich

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

3 lata do 39 lat (Dziecko, Dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

  • Patients must have one of the following histologically confirmed diagnoses (histologic confirmation from initial diagnosis acceptable, as appropriate):

    • Stratum A: Newly diagnosed diffuse intrinsic pontine glioma (WHO grade II-IV) - this stratum does not require tissue confirmation at time of enrollment, but diagnostic confirmation will be required to continue on study after biopsy. Patients with newly diagnosed DIPG will be eligible to enroll before or after standard of care radiation, but must be eligible for a biopsy. Newly diagnosed DIPG stratum should not have received prior therapy before the initiation of fimepinostat, with the exception of those patients who received temozolomide during radiation therapy or who previously received radiation as per standard of care and have not yet undergone a biopsy. All patients who have received therapy other than radiation and temozolomide should be discussed with study chair(s) prior to enrollment. Patients enrolling after standard of care radiation must be enrolled within 14 weeks of completion of radiotherapy.

    • Stratum B: Recurrent medulloblastoma (WHO grade IV), any molecular subtype

    • Stratum C: Recurrent high-grade glioma (HGG), including anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV)

      • Stratum B & C: Patients in the recurrent medulloblastoma or recurrent HGG arm can have locally recurrent or disseminated disease, provided resection/biopsy would still be clinically indicated. Disseminated disease can be diagnosed by imaging or Cerebrospinal fluid (CSF) cytology. Recurrent DIPG will be eligible for stratum C; however, eligibility requires biopsy/resection is feasible in a region of tumor outside of the pons (i.e. cerebellar extension or new metastatic site). These patients should be discussed with study chair(s) prior to enrollment

  • Patients must be able to swallow intact fimepinostat capsules or mini-tabs without chewing or crushing

  • Patients must have body surface area (BSA) >= 0.5 m^2

  • Patients must undergo tumor tissue collection as part of their standard of care

    • Minimum possible tissue collected must be equivalent to about 4-6 stereotactic core biopsies

  • Prior Therapy: Patients in the medulloblastoma and HGG strata will be allowed to have undergone prior therapy including surgery, chemotherapy, and radiation therapy. Patients in the newly diagnosed DIPG stratum should not have received prior therapy before the initiation of fimepinostat, with the exception of those patients who received temozolomide during radiation therapy or who previously received radiation as per standard of care and have not yet undergone a biopsy. All patients who have received therapy other than radiation and temozolomide should be discussed with study chair(s) prior to enrollment. Patients must have fully recovered from acute side effects related to previous anti-cancer therapies. Patients undergoing radiation during protocol therapy will not be permitted to receive other concomitant agents with radiation and pending initiation of maintenance with fimepinostat

    • Myelosuppressive chemotherapy: At least 21 days after last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)

    • Hematopoietic growth factors: At least 14 days after last dose of a long-acting growth factor or 7 days after short-acting growth factor or beyond time during which adverse events are known to occur

    • Biologic (anti-neoplastic agent): At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur

    • Monoclonal antibodies: At least 21 days after last dose of monoclonal antibody

    • Radiotherapy:

      • At least 2 weeks after local palliative radiotherapy (XRT)
      • At least 3 months from craniospinal XRT, or XRT to > 50% pelvis

    • Surgery:

      • At least 21 days from major surgery (biopsy and central line placement/removal are not considered major)

  • Corticosteroids: Subjects who are receiving dexamethasone must be on a stable or decreasing dose for at least 7 days prior to enrollment

  • 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)

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 milliliters (mL)/minute (min)/1.73 m^2 or

  • A serum creatinine based on age/gender as follows:

    • Age: Maximum Serum Creatinine (mg/dL)
    • 3 to < 6 years: 0.8 (male), 0.8 (female)
    • 6 to < 10 years: 1 (male), 1 (female)
    • 10 to < 13 years: 1.2 (male), 1.2 (female)
    • 13 to < 16 years: 1.5 (male), 1.4 (female)
    • >= 16 years: 1.7 (male), 1.4 (female)

  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age

  • Serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 110 U/L

  • Serum albumin >= 2 g/dL

  • Neurologic function:

    • Subjects with seizure disorder may be enrolled if well controlled

  • Gastrointestinal function:

    • Diarrhea < grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0

  • Metabolic function:

    • Non-fasting glucose < 125 mg/dL without the use of antihyperglycemic agents

      • If non-fasting glucose > 125 mg/dL, a fasting glucose should be done. If fasting glucose =< 160 mg/dL without the use of antihyperglycemic agents, patient will meet adequate metabolic function criteria

  • Cardiac function: corrected QT (QTc) < 480 msec

  • The effects of fimepinostat on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 30 days after completion of fimepinostat administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

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

Exclusion Criteria:

  • Subjects who have not recovered from acute adverse events due to therapeutic agents administered more than 4 weeks earlier
  • Patients must not have received prior therapy with single-agent or combination histone deacetylase (HDAC) and Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors
  • Subjects who are receiving any other investigational agent
  • History of allergic reaction to compounds of similar chemical or biological composition to fimepinostat
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
  • Patients with active human immunodeficiency virus (HIV) infection and with potential life-threatening consequences associated with immune-suppressive therapy
  • Patients with history of type 1 or 2 diabetes mellitus
  • Patients with gastrointestinal condition that could interfere with absorption or metabolism of fimepinostat

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Treatment (fimepinostat, tumor resection)

Patients receive fimepinostat by mouth once daily, on Days -2 to 0. Within 2 hours of receiving fimepinostat on Day 0, patients undergo tumor resection or biopsy as part of their standard of care.

MAINTENANCE PHASE: Patients receive fimepinostat by mouth, once daily for days 1-5 each week. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 12 months from the time treatment begins. Should patients continue to derive clinical benefit, and not experience excess toxicity or progression, patients can continue to receive drug for up to 24 months or longer pending discussion with study chairs and study sponsor.
Procedura: Therapeutic Conventional Surgery

Undergo surgery

Lek: Fimepinostat

Fimepinostat capsules

Inne nazwy:
  • CUDC-907

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Penetration of fimepinostat across the blood brain barrier (BBB)
Ramy czasowe: During surgery or biopsy

Will be analyzed using descriptive statistics from results of fimepinostat concentrations measured within the tumor tissue collected at the time of a standard of care surgery or biopsy. Within each strata, Simon's two-stage design will be used.
During surgery or biopsy

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Sabine Mueller, MD, PhD

Współpracownicy

Curis, Inc.
Cannonball Kids' Cancer Foundation
Pediatric Neuro-Oncology Consortium

Śledczy

  • Główny śledczy: Sabine Mueller, MD, PhD, University of California, San Francisco

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

7 sierpnia 2019

Zakończenie podstawowe (Rzeczywisty)

31 października 2022

Ukończenie studiów (Rzeczywisty)

28 października 2026

Daty rejestracji na studia

Pierwszy przesłany

26 marca 2019

Pierwszy przesłany, który spełnia kryteria kontroli jakości

26 marca 2019

Pierwszy wysłany (Rzeczywisty)

28 marca 2019

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

2 listopada 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

28 października 2026

Ostatnia weryfikacja

1 października 2026

Więcej informacji

Terminy związane z tym badaniem

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 18086
  • NCI-2019-00144 (Inny identyfikator: NCI Clinical Trials Reporting Program (CTRP))
  • PNOC016 (Inny identyfikator: Pediatric Neuro-Oncology Consortium)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

Individual participant data after de-identification

Typ informacji pomocniczych dotyczących udostępniania IPD

  • PROTOKÓŁ BADANIA

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

produkt wyprodukowany i wyeksportowany z USA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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