EZH102: Tazemetostat in Children and Young Adults with Synovial Sarcoma or INI1-Negative Tumors

A Phase I Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects with Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma

Categories:

Brain Tumor

Solid Tumor

Phase I/II

Diseases Treated:

Eligibility Overview:

  • Between 6 months and 21 years old
  • Relapsed or refractory rhabdoid tumors, INI1-negative tumors or synovial sarcoma
  1. Brief Summary

    This study will evaluate the investigational drug tazemetostat in treating recurrent or refractory pediatric INI1-negative tumors, rhabdoid tumors or synovial sarcoma. Patients with these tumors have few treatment options. Overall, the prognosis is poor for most patients with aggressive tumors that recur or are resistant to therapy.

    Tazemetostat is an inhibitor of Enhancer of Zeste homolog 2, also known as EZH2. EZH2 mutation and/or over-expression has been observed in several cancer types. In addition to genetic alterations in EZH2 itself, genetic changes in other proteins can lead to an oncogenic dependency on EZH2 activity. 

    Researchers have tested tazemetostat in adults with certain tumors, but they have not established the maximum tolerated dose (MTD) or the recommended pediatric Phase II dose (RP2D) in children and young adults.

    Primary Objectives

    • To determine the maximum tolerated dose or the recommended Phase II dose of tazemetostat when administered in an oral suspension twice daily in children with relapsed or refractory rhabdoid tumors, INI1-negative tumors or synovial sarcoma
    • To evaluate the antitumor effectiveness of tazemetostat in children with relapsed or refractory atypical teratoid rhabdoid tumor (ATRT), non-ATRT rhabdoid tumors, INI1-negative tumors or synovial sarcoma

    Eligibility Criteria

    Inclusion criteria include:

    • Between 6 months and 21 years old
    • Relapsed or refractory disease:
      • Rhabdoid tumors:
        • Atypical teratoid rhabdoid tumor (ATRT)
        • Malignant rhabdoid tumor (MRT)
        • Rhabdoid tumor of kidney (RTK)
        • Selected tumors with rhabdoid features
      • INI1-negative tumors:
        • Epithelioid sarcoma
        • Epithelioid malignant peripheral nerve sheath tumor
        • Extraskeletal myxoid chondrosarcoma
        • Myoepithelial carcinoma
        • Renal medullary carcinoma
        • Other INI1-negative malignant tumors
      • Synovial sarcoma with a SS18-SSX rearrangement
    • Ineligible for standard or other effective treatment options
    • Lansky Performance Status greater than 50%
    • Prior treatment-related clinically significant toxicities are clinically stable or not clinically significant at time of enrollment

    Exclusion Criteria include:

    • Prior exposure to tazemetostat or other inhibitor of enhancer of EZH2
    • Actively being treated for another concurrent malignancy or less than 5 years from completion of treatment for another malignancy
    • Participated in another interventional clinical study and received investigational drug within 30 days or five half-lives, whichever is longer, prior to planned first dose of tazemetostat
    • Major surgery within two weeks prior to enrollment
    • Pregnant or nursing

    Study Design

    Phase 1, open-label, dose escalation and dose expansion study

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in and outside the U.S.

  2. About this study

    This clinical trial will test a new drug to treat children and young adults with certain kinds of tumors that have come back after treatment or did not respond to treatment. The new drug is called tazemetostat. It operates by stopping a gene called EZH2 from working. 

    Tazemetostat has been studied in the laboratory. In these tests, the drug slowed down the growth of or killed certain cancer cells. Tazemetostat has also been tested in adults with several types of cancer. Some of the participants in these studies got better. Others did not. Tazemetostat has not been used in children and young adults.

    Purpose of this clinical trial

    The main goal of this study is to determine how much tazemetostat can safely be given to children and young adults. Researchers also want to know the good and bad effects of the drug and how it affects cancer cells. The study results may help doctors develop new and better treatments for future cancer patients.

    Eligibility overview

    • Between 6 months and 21 years old
    • Relapsed or refractory rhabdoid tumors, INI1-negative tumors or synovial sarcoma
  3. EZH102 Quick View
    Sponsors Epizyme, Inc.
    ClinicalTrials.gov identifier NCT02601937
    Trial Start Date December 2015
    Estimated Enrollment 108 worldwide (10 at St. Jude)
    Study Type Interventional
    Study Phase Phase I
    Conditions Rhabdoid tumors, INI1-negative tumors, synovial sarcoma, malignant rhabdoid tumor of ovary
    Ages Between 6 months and 21 years old
    Principal investigator Giles Robinson, MD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss EZH102 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Giles Robinson, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

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