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Report for Clinical Trial NCT02717455

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Phase 1 Trial of Panobinostat in Children With Diffuse Intrinsic Pontine Glioma

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.

NCT02717455 Glioma
MeSH: Glioma
HPO: Glioma

1 Interventions

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: Drug

Treatment (STRATUM 1) Treatment (STRATUM 2)


Primary Outcomes

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 collections

Description: 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 collections

Secondary Outcomes

Description: 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 12

Purpose: Treatment

Allocation: Non-Randomized

Sequential Assignment


There is one SNP

SNPs


1 K27M

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 ---



HPO Nodes


HPO:
Glioma
Genes 50
TSC2 GLI3 BRCA2 TSC1 LRP5 MLH1 PMS2 APC IDH1 MSH6 POT1 TSC2 CDKN2A NF2 MSH3 MSH6 APC NF1 EPCAM TSC1 TGFBR2 SEMA4A IDH1 IDH2 FAN1 APC MSH3 BMPR1A KRAS MLH1 MSH2 C11ORF95 PMS2 MLH3 PIK3CA NBN RELA SETBP1 IFNG RPS20 NF1 PMS1 CHEK2 APC TP53 MSH2 NBN ERBB2 APC NF2