This phase 2 trial will evaluate the activity of Panobinostat in combination with Everolimus for children with gliomas harboring H3.1 or H3.3K27M mutation, including newly diagnosed high-grade glioma or DIPG (diffuse intrinsic pontine glioma) after radiation (stratum A) and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).
Name: Panobinostat
Description: 30 mg/m^2Type: DrugPanobinostat and Everolimus
Name: Everolimus
Description: 3.0 mg/m^2Type: DrugPanobinostat and Everolimus
Description: Median PFS at 1 year for stratum A will be measured. Progression is defined as > 25% increase in the size of the tumor or appearance of new lesions.
Measure: Median Progression Free Survival (PFS) at 1 Year Time: 1yearDescription: Median PFS at 1 year for stratum A will be measured. Progression is defined as > 25% increase in the size of the tumor or appearance of new lesions.
Measure: Median Progression Free Survival (PFS) at 2 Years Time: 2yearsDescription: The proportion of patients alive at 1 year for stratum A.
Measure: Overall Survival at 1Year Time: 1yearDescription: The proportion of patients alive at 2 years for stratum A.
Measure: Overall Survival at 2Years Time: 2yearsDescription: Overall Response Rate (ORR) After Two Cycles of Panobinostat + Everolimus for stratum B. Overall response is defined as a partial or complete response. Partial response is defined as a ≥50% decrease in size of tumor in comparison to baseline measurements. Complete response is defined as the disappearance of all abnormal signal. This includes return to normal size of the brainstem for brainstem lesions.
Measure: Overall Response Rate (ORR) After Two Cycles of Panobinostat + Everolimus Time: 84 DaysSingle Group Assignment
There is one SNP
A Phase 2 Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas Harboring H3.3 or H3.1 K27M Mutation. --- K27M ---
- H3K27M mutation: Participants must have a mutation in H3.3 K27M or H3.1 K27M as identified by tumor (FFPE or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing, or by CLIA-certified immunohistochemistry staining positive for H3K27M, as defined by review by U of M neuro-pathology. --- K27M ---
- H3K27M mutation: Participants must have a mutation in H3.3 K27M or H3.1 K27M as identified by tumor (FFPE or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing, or by CLIA-certified immunohistochemistry staining positive for H3K27M, as defined by review by U of M neuro-pathology. --- K27M --- --- K27M ---