Fimepinostat in Treating Brain Tumors in Children and Young Adults (PNOC016)

A Target Validation Study of Fimepinostat in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG), Recurrent Medulloblastoma, or Recurrent High-Grade Glioma (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.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Glioblastoma; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Diffuse Intrinsic Pontine Glioma; Recurrent Anaplastic Astrocytoma
• Intervention / Treatment: Procedure: Therapeutic Conventional Surgery; Drug: Fimepinostat

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 39 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Procedure: Therapeutic Conventional Surgery; Undergo surgery; Drug: Fimepinostat; Fimepinostat capsules; Other Names: CUDC-907

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Penetration of fimepinostat across the blood brain barrier (BBB)	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

Collaborators and Investigators

• Sponsor: Sabine Mueller, MD, PhD
• Collaborators: Curis, Inc.; Cannonball Kids' Cancer Foundation; Pediatric Neuro-Oncology Consortium
• Investigators: Principal Investigator: Sabine Mueller, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2019
• Primary Completion (Actual): October 31, 2022
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neuroectodermal Tumors, Primitive; Central Nervous System Neoplasms; Brain Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Diffuse Intrinsic Pontine Glioma; Recurrence; Glioblastoma; Glioma; Astrocytoma; Medulloblastoma
• Other Study ID Numbers: 18086; NCI-2019-00144 (Other Identifier: NCI Clinical Trials Reporting Program (CTRP)); PNOC016 (Other Identifier: Pediatric Neuro-Oncology Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data after de-identification
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No