PBTC47: A Clinical Trial of the Drug, Panobinostat, in Children with Brain Tumors (CLOSED TO ACCRUAL)

Brief Summary

Diffuse intrinsic pontine glioma, also known as DIPG, comprises approximately 10-15% of pediatric brain tumors and is the most common tumor subtype in the brainstem. An aggressive tumor, DIPG is the leading cause of childhood brain tumor death.

Current therapies are largely ineffective. Surgical resection is not possible because DIPG grows diffusely and infiltrates critical brainstem structures. Radiation therapy has remained the mainstay of treatment for the past three decades since its introduction, but relapse generally occurs in most patients.

This is a Phase I study of panobinostat in children with recurrent or progressive DIPG. Panobinostat is a pan-HDAC inhibitor of Class I, II and IV histone deacetylases (HDACs). Pre-clinical evidence suggests patient-derived DIPG cell lines are sensitive to HDAC inhibitors in the lab. Although panobinostat has been approved by the U.S. Food and Drug Administration for use in adults with multiple myeloma, it has not been approved for use in children. 

Primary Objectives

• To describe the toxicity profile and define the dose-limiting toxicities of panobinostat in children with recurrent/progressive DIPG.
• To estimate the maximum-tolerated dose and/or the recommended-phase 2 dose of panobinostat in children with recurrent/progressive DIPG.
• To evaluate and characterize the plasma pharmacokinetics of panobinostat in children with recurrent/progressive DIPG 1.2

Eligibility Criteria

Inclusion Criteria Include:

• Diagnosis of progressive DIPG or an increase in the bi-dimensional measurement or the appearance of a new tumor lesion since diagnosis
• At least 2 but not more than 22 years old
• Able to swallow capsules whole
• Must have received at least 54 Gy focal irradiation administered over approximately 42 days prior to study enrollment

Exclusion Criteria Include:

• More than 60 Gy total radiation to the pons
• Prior HDAC, DAC, HSP90 inhibitors for treatment of DIPG
• Valproic acid within 28 days prior to enrollment
• Prior bone marrow transplant

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

Collaborating sites in the U.S.

About this study

Diffuse intrinsic pontine glioma, also known as DIPG, is a tumor that starts in the brain stem above the back of the neck. DIPG is a very stubborn cancer. It is hard to treat because it is located in a very sensitive area of the body that controls breathing and other important functions. In most cases, doctors do not want to operate on a tumor in this part of the body because of the risk to the brain. Most doctors recommend treatment with high-energy X-rays or other type of radiation. Treatment may also include chemotherapy. Even with these treatments, the number of children who survive DIPG is very low.

Researchers are studying new drugs that may do a better job of fighting this type of cancer. One of these experimental drugs is called panobinostat. This drug has been approved by the U.S. Food and Drug Administration (FDA) for use in adults with a type of cancer called multiple myeloma but has not been approved for children. Its use for children with DIPG is considered experimental.

Based on laboratory and animal studies, researchers believe panobinostat may kill DIPG tumor cells. 

Purpose of this observational study

The main goal of this study is to find out if children with DIPG can safely take panobinostat and learn the best dose that will kill their tumors. Researchers also want to learn what kinds of side effects happen in children with DIPG when they take this drug and how their bodies handle this drug.

Eligibility overview

• Diagnosis of DIPG
• At least 2 but not more than 22 years old
• Able to swallow capsules whole