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Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Participants receive panobinostat nanoparticle formulation MTX110 IT by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Panobinostat Nanoparticle Formulation MTX110

Convection-Enhanced Delivery (CED)

Sabine Mueller, M.D.

This phase I/II trial studies the side effects of panobinostat nanoparticle formulation MTX110 (MTX110) in treating participants with newly-diagnosed diffuse intrinsic pontine glioma. Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of repeated administration of MTX110 co-infused with gadoteridol given by intratumoral convection enhanced delivery in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

SECONDARY OBJECTIVES:

I. To determine the clinical efficacy of repeated administration of MTX110 given by intratumoral convection-enhanced delivery (CED) in children with newly diagnosed DIPG in the confines of a phase I and early efficacy study.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Participants receive panobinostat nanoparticle formulation MTX110 intratumorally (IT) by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment participants are followed up at 30 days and then every 2 months.

MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma

An Open Label Single Arm Phase I/II Study of MTX110 Delivered by Convection-enhanced Delivery (CED) in Patients With Diffuse Intrinsic Pontine Glioma (DIPG) Previously Treated With External Beam Radiation Therapy

Adverse events and clinically significant laboratory abnormalities which meet Grade 3, 4, or 5 criteria according to Common Terminology Criteria for Adverse Events (CTCAE) classified by investigators and treating physicians as related to study treatment (probable, possible, and definite) will be summarized by maximum intensity/grade. Adverse events will be graded according to CTCAE version 4.0.

Overall survival is defined as the percentage of participants alive from time of diagnosis up to 12 months.

Midatech Pharma US Inc.

Pacific Pediatric Neuro-Oncology Consortium

Sabine Mueller, MD, PhD

Assistant Professor of Clinical Neurology

Additional adverse event and mortality data was collected for participants for up to 24 months following initial diagnosis. While individual participants were assigned to receive separate doses, participants are presented in one Arm/Group due to confidentiality concerns for this rare disease study.

Participants receive panobinostat nanoparticle formulation MTX110 IT by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Panobinostat Nanoparticle Formulation MTX110: Given IT

Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Treatment (MTX110)

Participants receive panobinostat nanoparticle formulation MTX110 IT by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Treatment (MTX110) - All Participants

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

While individual participants were assigned to receive separate doses, participants are presented in one Arm/Group due to confidentiality concerns for this rare disease study

Phase 2 expansion cohort was not activated at behest of pharmaceutical supplier.

Dr. Sabine Mueller, MD, PhD.

Muscle weakness right-sided (Grade 3)

Stridor (Grade 3)

Vagus nerve disorder (Grade 3)

Gait disturbance (Grade 3)

Neutrophil count decreased (Grade 3)

Proportion of Participants With Grade 3 or Higher, Treatment-related, Adverse Events

Overall Survival Rate (OS) at 12 Months

Participant received starting dose of single CED of 30 micrometer of MTX110 on 1 day (day 1); Total volume 3 mL. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 1 (MTX110)

Participant received starting dose of repeated CED of 30 micrometer of MTX110 on n 2 consecutive days (days 1, 2); Total volume 6 mL (3 mL on each day).

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 2 (MTX110)

Participant received starting dose of repeated CED of 30 micrometer of MTX110 on n 2 consecutive days (days 1, 2); Total volume 8 mL (4 mL on each day).

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 3 (MTX110)

Participant received starting dose of repeated CED of 30 micrometer of MTX110 on n 2 consecutive days (days 1, 2); Total volume 10 mL (5 mL on each day).

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 4 (MTX110)

Participant received starting dose of repeated CED of 30 micrometer of MTX110 on n 2 consecutive days (days 1, 2); Total volume 12 mL (6 mL on each day).

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 5 (MTX110)

Participant received starting dose of repeated CED of 60 micrometer of MTX110 on n 2 consecutive days (days 1, 2); Total volume 12 mL (6 mL on each day).

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 6 (MTX110)

Participant received starting dose of repeated CED of 90 micrometer of MTX110 on n 2 consecutive days (days 1, 2); Total volume 12 mL (6 mL on each day).

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

Phase 1: Starting Dose Level 7 (MTX110)

Participants will receive Recommended Phase 2 Dose (RP2D)

Panobinostat Nanoparticle Formulation MTX110: Given IT Convection-Enhanced Delivery (CED): Undergo CED

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