SJPI3K: Phase I Study of GDC-0084 in Young Patients with Newly Diagnosed DIPG or other Gliomas after Radiation Therapy

Phase I Study of GDC-0084, a Brain-Penetrant PI3 Kinase/mTOR Inhibitor, in Pediatric Patients with Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or Other Diffuse Midline Gliomas after Radiation Therapy

Categories:

Brain Tumor

Phase I/II

Diseases Treated:

DIPG, diffuse midline glioma, H3 K27M-mutant glioma

Eligibility Overview:

  • Between 2 and 22 years old
  • Diagnosed with diffuse intrinsic pontine glioma (DIPG) or other midline glioma that has not spread
  • No prior therapy, other than surgery and/or steroids
  1. Brief Summary

    Genetic alterations activating the PI3K pathway are common in pediatric patients with diffuse midline glioma. This Phase I clinical trial will evaluate GDC-0084, a selective small-molecule inhibitor of class I PI3K and mTOR kinase, in pediatric patients with newly diagnosed DIPG or other diffuse midline glioma after standard-of-care radiation therapy. GDC-0084 is designed to efficiently cross the blood-brain barrier to achieve high drug exposure in the brain.

    Preclinical studies have shown GDC-0084 to be effective in inhibiting the PI3K signaling pathway and tumor growth in PI3K-activated brain tumor models. A Phase I study has been completed in adult patients with high grade glioma and a Phase II randomized study in adults with newly diagnosed high grade glioma is ongoing. This study will be the first time GDC-0084 is evaluated in children.

    Primary Objective

    • To estimate the maximum tolerated dose (MTD) and/or the recommended Phase II dose of GDC-0084 in pediatric patients with newly diagnosed DIPG and other diffuse midline glioma
    • To determine toxicities associated with GDC-0084 in the pediatric population
    • To characterize the pharmacokinetics of GDC-0084 in the pediatric population

    Eligibility Criteria

    Inclusion criteria include:

    • At least 2 years old and younger than 22 years old
    • Newly diagnosed DIPG or diffuse midline glioma, H3 K27M-mutant
    • Localized, non-metastatic disease
    • Able to begin radiation therapy no later than 42 days after radiographic diagnosis or surgery, whichever is later
    • No prior therapy, other than surgery and/or steroids

    Exclusion Criteria include:

    • Evidence of tumor infiltration of three or more cerebral lobes on diagnostic MRI
    • Requires insulin therapy
    • History of clinically significant, uncontrolled heart disease and/or repolarization abnormalities
    • Pregnant or breastfeeding
    • Unable to return for follow-up visits

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

  2. About this study

    This is a Phase I clinical trial for children, adolescents and young adults with DIPG tumors and similar midline gliomas with an H3 K27M mutation. DIPG tumors occur in a part of the brain called the brain stem. These cancerous tumors are usually treated with radiation therapy, but the tumors often come back after treatment or do not respond to the radiation at all.

    This study will test a new, experimental drug to be given to patients after radiation therapy. This anti-cancer drug is called GDC-0084. It is considered experimental because it has not yet been approved by the U.S. Food and Drug Administration (FDA) to treat cancer.

    Many drugs do a poor job of fighting brain tumors because they do not cross the blood brain barrier, the brain’s defense system of cells that prevents substances from reaching the brain. GDC-0084 is able to cross this barrier and has been shown to be effective against brain tumors in the laboratory and in animals. However, the drug has been given only to a small number of adults and there is a lot that we do not know about it yet. This study will be the first time GDC-0084 is given to children.

    Purpose of this clinical trial

    The main goal of this study is to find out if GDC-0084 is safe for children, adolescents and young adults with DIPG and similar tumors.  Researchers also want to learn more about the good and bad effects of the drug.

    Eligibility overview

    • Between 2 and 22 years old
    • Diagnosed with DIPG or other midline glioma that has not spread
    • No prior therapy, other than surgery and/or steroids
  3. SJPI3K Quick View
    Sponsors St. Jude Children's Research Hospital
    Collaborator Kazia Therapeutics
    ClinicalTrials.gov identifier NCT03696355
    Trial Start Date October 2018
    Estimated Enrollment 41
    Study Type Interventional
    Study Phase Phase I
    Conditions DIPG, midline glioma
    Ages 2 to 22 years old
    Principal investigator Christopher Tinkle, MD, PhD
    Co-principal investigator Amar Gajjar, MD
    Co-investigator Suzanne (Suzy) Baker, PhD
    Study Sites St. Jude Children’s Research Hospital
    For a consultation or to discuss SJPI3K St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 901-595-2544 or 901-595-4599
Fax: 901-595-6211

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: (901) 595-2544
FAX: (901) 595-6211

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.