Phase I trial of panobinostat in children with diffuse intrinsic pontine glioma: A report from the Pediatric Brain Tumor Consortium (PBTC-047)

Michelle Monje*, Tabitha Cooney, John Glod, Jie Huang, Cody J. Peer, Damien Faury, Patricia Baxter, Kim Kramer, Alicia Lenzen, Nathan J. Robison, Lindsay Kilburn, Anna Vinitsky, William D. Figg, Nada Jabado, Maryam Fouladi, Jason Fangusaro, Arzu Onar-Thomas, Ira J. Dunkel, Katherine E. Warren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood cancer with median survival of less than 1 year. Panobinostat is an oral multihistone deacetylase inhibitor with preclinical activity in DIPG models. Study objectives were to determine safety, tolerability, maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics of panobinostat in children with DIPG. Patients and Methods: In stratum 1, panobinostat was administered 3 days per week for 3 weeks on, 1 week off to children with progressive DIPG, with dose escalation following a two-stage continual reassessment method. After this MTD was determined, the study was amended to evaluate the MTD in children with nonprogressive DIPG/Diffuse midline glioma (DMG) (stratum 2) on an alternate schedule, 3 days a week every other week in an effort to escalate the dose. Results: For stratum 1, 19 subjects enrolled with 17/19 evaluable for dose-finding. The MTD was 10 mg/m2/dose. Dose-limiting toxicities included thrombocytopenia and neutropenia. Posterior reversible encephalopathy syndrome was reported in 1 patient. For stratum 2, 34 eligible subjects enrolled with 29/34 evaluable for dose finding. The MTD on this schedule was 22 mg/m2/dose. DLTs included thrombocytopenia, neutropenia, neutropenia with grade 4 thrombocytopenia, prolonged intolerable nausea, and increased ALT. Conclusions: The MTD of panobinostat is 10 mg/m2/dose administered 3 times per week for 3 weeks on/1 week off in children with progressive DIPG/DMG and 22 mg/m2/dose administered 3 times per week for 1 week on/1 week off when administered in a similar population preprogression. The most common toxicity for both schedules was myelosuppression.

Original languageEnglish
Pages (from-to)2262-2272
Number of pages11
Issue number12
StatePublished - 1 Dec 2023
Externally publishedYes


  • DIPG
  • HDAC inhibitors
  • brainstem glioma
  • epigenetics
  • midline glioma


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