This phase I trial studies the side effects and best dose of panobinostat in treating younger patients with diffuse intrinsic pontine glioma (DIPG). Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stratum 1 treats patients with DIPG that has returned or gotten worse (progressed). Stratum 2 treats patients with DIPG that has not yet gotten worse. Currently, only Stratum 2 is enrolling patients.
Name: LBH589
Description: STRATUM 1: Recurrent/progressive DIPG. Panobinostat will be given every other day, 3 times/ week, p.o. preferably on Mon/Wed/Fri, for three weeks, followed by one week off of therapy. Three weeks of therapy plus the one week rest period (4 weeks) will constitute one course. Treatment will continue for up to 26 courses (about 2 years) barring progressive disease or unacceptable toxicity. STRATUM 2: Non-progressed DIPG. Panobinostat will be given every other day, 3 times/week, every other week p.o. preferably on Mon/Wed/Fri. Four weeks will constitute one course. Treatment will continue for up to 26 courses (about 2 years) unless the patient experiences progressive disease, unacceptable toxicity or any of the off-treatment criteria.Type: DrugTreatment (STRATUM 1) Treatment (STRATUM 2)
Description: Adverse Events
Measure: To describe the toxicity profile and the dose-limiting toxicities of panobinostat in children with recurrent/progressive DIPG Time: 26 courses (approximately 2 years)Description: Dose Finding
Measure: To estimate the maximum-tolerated dose and/or the recommended-phase 2 dose of panobinostat in children with recurrent/progressive DIPG Time: Course 1 (the first 4 weeks of treatment)Description: Plasma Pharmacokinetics
Measure: To evaluate and characterize the plasma pharmacokinetics of panobinostat in children with recurrent/progressive DIPG Time: Course 1, Day 1 and Day 3 sample collectionsDescription: Adverse Events
Measure: To describe the toxicity profile and define the dose-limiting toxicities of panobinostat in children with non-progressed DIPG treated with 3 times/week, every other week. Time: 26 courses (approximately 2 years)Description: Dose Finding
Measure: To estimate the maximum-tolerated dose and/or the recommended-phase 2 dose of panobinostat administered 3 times/week, every other week in children with non-progressed DIPG Time: Course 1 (the first 4 weeks of treatment)Description: Plasma Pharmacokinetics
Measure: To evaluate and characterize the plasma pharmacokinetics of panobinostat administered 3 times/week, every other week in children with non-progressed DIPG Time: Course 1, Day 1 and Day 3 sample collectionsDescription: Evaluated Response per imaging or clinical progression
Measure: To describe the progression-free survival (PFS) and overall survival (OS) of children with recurrent or progressive DIPG who are treated with panobinostat Time: 26 courses (approximately 2 years)Description: Evaluated Response per imaging or clinical progression
Measure: To describe the progression-free survival (PFS) and overall survival (OS) of children with non-progressed DIPG who are treated with panobinostat Time: 26 courses (approximately 2 years)Description: Pharmacodynamics: Cell-free DNA - Blood and Urine (Optional)
Measure: To identify histone 3 K27M mutations in peripheral blood and urine, and evaluate changes with treatment. Time: Day 1 of courses 1, 2, 4, 6, and 12Allocation: Non-Randomized
Sequential Assignment
There is one SNP
To identify histone 3 K27M mutations in peripheral blood and urine, and evaluate changes with treatment.. Pharmacodynamics: Cell-free DNA - Blood and Urine (Optional). --- K27M ---
Based on the in vitro and in vivo activity of panobinostat in preclinical models using DIPG cell cultures and orthotopic xenograft model systems, and the potentially important role of histone deacetylases and histone 3 K27M mutations in relation to pontine malignancies, the investigators are conducting a Phase 1 study of panobinostat in children with recurrent/progressive DIPG. --- K27M ---