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

Phase I study of Savolitinib in Recurrent, Progressive or Refractory Medulloblastoma, High-Grade Glioma, or Diffuse Intrinsic Pontine Glioma

Categories:

Brain Tumor

Phase I/II

Diseases Treated:

Medulloblastoma

High-grade glioma (HGG)

Diffuse intrinsic pontine glioma (DIPG)

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
  1. 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.
  2. 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
  3. PBTC49 Quick View
    Sponsors: Pediatric Brain Tumor Consortium
    ClinicalTrials.gov identifier NCT03598244
    Trial Start Date: July 2018
    Estimated Enrollment: 5 (at St. Jude)
    Study Type: Interventional
    Study Phase: Phase I
    Conditions: Medulloblastoma, HGG, DIPG
    Ages: 5 to 21 years old
    Principal investigator at St. Jude: Anna Vinitsky, MD, MS
    Study Sites: St. Jude Children’s Research Hospital and collaborating sites in the U.S.
    For a consultation or to discuss PBTC49: St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Anna Vinitsky, MD, MS
St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 1-888-226-4343 or 901-595-4055
Email: referralinfo@stjude.org