PBTC49: Study of Savolitinib in Recurrent, Progressive or Refractory Medulloblastoma, HGG or DIPG

Brief Summary

Mesenchymal epithelial transition receptor (c-MET) is an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). MET has a normal function in organ development during embryogenesis and in tissue homeostasis during adult life.  Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET triggers tumor growth, angiogenesis and metastasis.

Savolitinib (volitinib) is a potent and selective small molecule inhibitor of c-MET kinase at the cellular and enzymatic levels. In preclinical studies, savolitinib demonstrated strong in vitro and in vivo activity against c-MET kinases and downstream signaling targets and significantly decreased tumor cell growth.

This is a dose escalation study of savolitinib given orally once a day to patients with recurrent, progressive or refractory central nervous system tumors.

Primary Objectives

•  To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of savolitinib administered once daily in children with refractory, progressive or recurrent primary CNS tumors
• To define and describe toxicities of savolitinib in these patients
• To characterize the pharmacokinetics of savolitinib in these patients

Eligibility Criteria

Inclusion criteria include:

• Recurrent, refractory or progressive medulloblastoma, HGG or DIPG
• Evidence of genetic activation of the MET pathway (expansion co-hort)
• At least 5 years old and 21 years old or younger
• Failed prior standard therapy
• Adequate organ and marrow function
• Not pregnant

Exclusion Criteria include:

• Breast-feeding
• Known serious active infection
• Uncontrolled hypertension
• Receiving other anticancer or investigational drug therapy
• History of other malignancy, except secondary brain tumor if first malignancy has been in remission at least 5 years from end of treatment

Study Sites

• St. Jude Children’s Research Hospital, Memphis, Tennessee
• Collaborating sites in the U.S.
  

About this study

This is a clinical research study for children and young adults with brain cancer that has grown or come back after standard therapy.

The drug in this study is called savolitinib (volitinib). It is considered an experimental drug that has been tested in adults with advanced solid tumors. There is scientific reason to believe it may work against brain tumors.  However, we have not yet found the safe dose for children or proven that the drug works for brain tumors. This trial is being conducted to see if savolitinib is safe and tolerable in children with brain tumors.

Purpose of this clinical trial

Eligibility overview

• Recurrent, refractory or progressive medulloblastoma, high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG)
• Evidence of genetic activation of the MET pathway (expansion co-hort)
• At least 5 years old and 21 years old or younger