Clinical Trial
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)
Please note, this study has closed to accrual and is no longer accepting patients. || This study will include children and young adults (3-39 years of age) with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG who will undergo tissue collection as part of standard of care. Patients will initiate drug prior to resection/biopsy and continue drug during a maintenance phase after resection/biopsy. Fimepinostat is a pan-HDAC and PI3K inhibitor. Fimepinostat will be given orally 2 days prior to resection/biopsy and the day of the resction/biopsy (for a total of 3 doses). Treatment with fimepinostat CUDC-907 will continue during a maintenance phase after resection/biopsy once daily for 5 daily doses every week. Patients will receive fimepinostat on study 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.
Despite advances in neurosurgery, chemotherapy, and radiotherapy, outcomes remain poor for many pediatric brain tumors, such as DIPG, MYC-driven medulloblastoma, and HGG. Due to continued poor outcomes, many studies have investigated novel therapeutic approaches targeting molecular pathways that are active in pediatric brain tumors. Two common molecular pathways involved in pediatric brain tumors include those in regulation of chromatin and MYC, a transcription factor mediating cell survival, division, and apoptosis. A range of histone deacetylase (HDAC) inhibitors are currently being studied to address altered chromatin remodeling, while phosphatidylinositol 3-kinase (PI3K) inhibitors are being used to decrease MYC overexpression.
A novel oral, potent dual pan-HDAC and PI3K inhibitor, fimepinostat, has shown broad antitumor activity in hematologic and solid tumors. Fimepinostat demonstrates greater inhibition of tumor growth in vitro and in vivo than single-target HDAC or PI3K inhibitors. Given the evidence of chromatin and PI3K-related activity among a range of pediatric brain tumors and the preclinical/clinical promise of fimepinostat, this drug holds promise as a successful treatment strategy for children and young adults with brain tumors.
To confirm penetration of fimepinostat across the blood brain barrier (BBB) in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG by measuring concentration of fimepinostat in tumor tissue
Funding is provided by Curis & Cannonball Kids Cancer.
Please note, this study has closed to accrual and is no longer accepting patients. || This study will include children and young adults (3-39 years of age) with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG who will undergo tissue collection as part of standard of care. Patients will initiate drug prior to resection/biopsy and continue drug during a maintenance phase after resection/biopsy. Fimepinostat is a pan-HDAC and PI3K inhibitor. Fimepinostat will be given orally 2 days prior to resection/biopsy and the day of the resction/biopsy (for a total of 3 doses). Treatment with fimepinostat CUDC-907 will continue during a maintenance phase after resection/biopsy once daily for 5 daily doses every week. Patients will receive fimepinostat on study 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.
Despite advances in neurosurgery, chemotherapy, and radiotherapy, outcomes remain poor for many pediatric brain tumors, such as DIPG, MYC-driven medulloblastoma, and HGG. Due to continued poor outcomes, many studies have investigated novel therapeutic approaches targeting molecular pathways that are active in pediatric brain tumors. Two common molecular pathways involved in pediatric brain tumors include those in regulation of chromatin and MYC, a transcription factor mediating cell survival, division, and apoptosis. A range of histone deacetylase (HDAC) inhibitors are currently being studied to address altered chromatin remodeling, while phosphatidylinositol 3-kinase (PI3K) inhibitors are being used to decrease MYC overexpression.
A novel oral, potent dual pan-HDAC and PI3K inhibitor, fimepinostat, has shown broad antitumor activity in hematologic and solid tumors. Fimepinostat demonstrates greater inhibition of tumor growth in vitro and in vivo than single-target HDAC or PI3K inhibitors. Given the evidence of chromatin and PI3K-related activity among a range of pediatric brain tumors and the preclinical/clinical promise of fimepinostat, this drug holds promise as a successful treatment strategy for children and young adults with brain tumors.
To confirm penetration of fimepinostat across the blood brain barrier (BBB) in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG by measuring concentration of fimepinostat in tumor tissue
Funding is provided by Curis & Cannonball Kids Cancer.
Sites Offering This Trial
- CHICAGO, IL Ann & Robert H. Lurie Children’s Hospital of Chicago
- LOS ANGELES, CA Children’s Hospital Los Angeles
- MINNEAPOLIS, MN Children’s Minnesota
- WASHINGTON, DC Children’s National Hospital
- BOSTON, MA Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
- PORTLAND, OR Doernbecher Children’s Hospital Oregon Health & Science University (OHSU)
- BALTIMORE, MD Johns Hopkins Hospital
- COLUMBUS, OH Nationwide Children’s Hospital
- MEMPHIS, TN St. Jude Children’s Research Hospital
- ST. LOUIS, MO St. Louis Children’s Hospital
- HOUSTON, TEXAS Texas Children’s Hospital*
- PHILADELPHIA, PA The Children’s Hospital of Philadelphia
- ZURICH, SWITZERLAND University Children’s Hospital Zürich
- San Francisco, CA UCSF Benioff Children’s Hospitals
- SEATTLE, WA Seattle Children’s Hospital
- GAINESVILLE, FL University of Florida Shands Children’s Hospital
- SAN DIEGO, CA University of California, San Diego Rady Children’s Hospital
- ANN ARBOR, MI University of Michigan – C.S. Mott Children’s Hospital
- SALT LAKE CITY, UT University of Utah
How to Enroll
If you believe your child or patient is eligible for this trial, contact the closest participating site or email us for more information.