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Eligibility
for people ages 16 years and up
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID administered orally in continuous 28 day cycles. Screening of subjects to determine eligibility for the study will be performed within 21 days of the first planned dose of tazemetostat. Eligible subjects will be enrolled into one of fivecohorts based on tumor type: - Cohort 1: MRT, RTK, ATRT, or selected tumors with rhabdoid features, including small cell carcinoma of the ovary hypercalcemic type [SCCOHT], also known as malignant rhaboid tumor of the ovary [MRTO] - Cohort 2: Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement - Cohort 3: Other INI1 negative tumors or any solid tumor with an EZH2 gain of function (GOF) mutation, including: epithelioid malignant peripheral nerve sheath tumor (EMPNST), extraskeletal myxoid chondrosarcoma (EMC), myoepithelial carcinoma, other INI1-negative malignant tumors with Sponsor approval (e.g., dedifferentiated chordoma) any solid tumor with an EZH2 GOF mutation including but not limited to Ewing's sarcoma and melanoma - Cohort 4: Renal medullary carcinoma (RMC) - Cohort 5: Epithelioid sarcoma (ES) Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study. Response assessment will be evaluated after 8 weeks of treatment and then every 8 weeks thereafter while on study.

Keywords

Malignant Rhabdoid Tumors (MRT) Rhabdoid Tumors of the Kidney (RTK) Atypical Teratoid Rhabdoid Tumors (ATRT) Selected Tumors With Rhabdoid Features Synovial Sarcoma INI1-negative Tumors Malignant Rhabdoid Tumor of Ovary Renal Medullary Carcinoma Epithelioid Sarcoma Any Solid Tumor With an EZH2 GOF Mutation

Eligibility

You can join if…

Open to people ages 16 years and up

  1. Age (at the time of consent/assent): ≥16 years of age
  2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  3. Has a life expectancy of>3 months
  4. Has a malignancy:

    • For which there are no standard therapies available (Cohorts 1, 3, 4 and 5)
    • That is relapsed or refractory after treatment with an approved therapy(ies),defined as metastatic or non-resectable, locally advanced disease that has previously been treated with and progressed following approved therapy(ies)(Cohort 2)
    • That has progressed within 6 months prior to study enrollment (Cohort 5 Expansion ONLY)
  5. Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA/College of American Pathologists(CAP) or equivalent laboratory certification
  6. For Cohort 1 (rhabdoid tumors only), the following test results must be available by local laboratory: morphology and immunophenotypic panel consistent with rhabdoid tumors, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss or mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
  7. For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
  8. For Cohort 3 to 5 (subjects with INI1-negative/aberrant tumors or any solid tumor with EZH2 GOF mutation only), the following test results must be available by local laboratory: Morphology and immunophenotypic panel consistent with INI1-negative tumors (not applicable for solid tumors with EZH2 GOF mutation), and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss or mutation when INI1 IHC is equivocal or unavailable, or molecular evidence of EZH2 GOF mutation
  9. Prior therapy(ies), if applicable, must be completed according to the criteria below:

    • Chemotherapy: cytotoxic (At least 21 days since last dose of chemotherapy prior to first dose of tazemetostat)
    • Chemotherapy: nitrosoureas (At least 6 weeks since last dose of nitrosoureas prior to first dose of tazemetostat)
    • Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) (At least 14 days since last dose of non-cytotoxic chemotherapy prior to first dose of tazemetostat)
    • Monoclonal antibody(ies) (At least 3 half-lives since the last dose of any monoclonal antibody prior to first dose of tazemetostat)
    • Immunotherapy (e.g. tumor vaccine) (At least 42 days since last dose of immunotherapy agent(s) prior to first dose of tazemetostat)
    • Radiotherapy (RT) (At least 14 days from last local site RT prior to first dose of tazemetostat/At least 21 days from stereostatic radiosurgery prior to first dose of tazemetostat/At least 12 weeks from craniospinal, ≥50% radiation of pelvis, or total body irradiation prior to first dose of tazemetostat)
    • High dose therapy with autologous hematopoietic cell infusion (At least 60 days from last infusion prior to first dose of tazemetostat)
    • Hematopoietic growth factor (At least 14 days from last dose of hematopoietic growth factor prior to first dose of tazemetostat)
  10. Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing of IHC and/or cytogenetics/FISH and/or DNA mutation analysis (required for study entry but enrollment based on local results)
  11. Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors
  12. Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function as defined by criteria below:

    • Hematologic (BM Function):
    • Hemoglobin ≥9 mg/dL
    • Platelets ≥100,000/mm^3 (≥100x10^9/L)
    • ANC ≥1,000/mm^3 (≥1.0x10^9/L)
    • Hematologic (Coagulation Factors):
    • PT and PTT <1.5 ULN
    • Fibrinogen>0.5 LLN
    • Renal Function:
    • Serum creatinine ≤1.5 x ULN
    • Hepatic Function:
    • Conjugated bilirubin <1.5 x ULN
    • AST and ALT <3 x ULN
  13. For subjects with ATRT only, subject must have seizures that are stable, not increasing in frequency or severity and controlled on current anti-seizure medication(s) for a minimum of 21 days prior to the planned first dose of tazemetostat
  14. Has a shortening fraction of>27% or an ejection fraction of ≥50% by echocardiogram(ECHO) or multi-gated acquisition (MUGA) scan and New York Heart Association (NYHA)Class ≤2
  15. Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec

You CAN'T join if...

  1. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
  2. Has participated in another interventional clinical study and received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the planned first dose of tazemetostat
  3. Has known active CNS or any leptomeningeal metastasis of primary extra-cranial tumor

    • NOTE: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging 4 weeks prior to the first dose of study drug and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and are on stable or tapering doses of steroids for at least 7 days prior to first dose of study drug.
  4. Has had a prior malignancy other than the malignancies under study - EXCEPTION: A subject who has been disease-free for 5 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible
  5. Has had major surgery within 3 weeks prior to enrollment
  6. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
  7. Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction,or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
  8. Is currently taking any prohibited medication(s)
  9. Has an active infection requiring systemic treatment
  10. Is immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV)
  11. Has known chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable HCV RNA)
  12. Has had a symptomatic venous thrombosis within the 3 months prior to study enrollment

    • NOTE: Subjects with a history of a deep vein thrombosis>2 weeks prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study
  13. For subjects with CNS involvement (primary tumor or metastatic disease), have any active bleeding or new intratumoral hemorrhage of more than punctuate size of screening MRI obtained within 14 days of starting study drug or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents

Locations

  • University of Colorado Denver accepting new patients
    Aurora, Colorado, 80045, USA
  • Mayo Clinic - Jacksonville accepting new patients
    Jacksonville, Florida, 32224, USA
  • Northwestern Memorial Hospital accepting new patients
    Chicago, Illinois, 60611, USA
  • Massachusetts General Hospital - Cancer Center accepting new patients
    Boston, Massachusetts, 02114, USA
  • Dana Farber Cancer Institute accepting new patients
    Boston, Massachusetts, 02215, USA
  • University of Michigan accepting new patients
    Ann Arbor, Michigan, 48109, USA
  • Washington University accepting new patients
    St. Louis, Missouri, 63130, USA
  • Memorial Sloan Kettering Cancer Center accepting new patients
    New York, New York, 10065, USA
  • Cincinnati Children's Hospital Medical Center accepting new patients
    Cincinnati, Ohio, 45229, USA
  • Oregon Health Sciences University accepting new patients
    Portland, Oregon, 97239, USA
  • MD Anderson Cancer Center accepting new patients
    Houston, Texas, 77030, USA
  • Seattle Children's Hospital accepting new patients
    Seattle, Washington, 98105, USA
  • Fred Hutchinson Cancer Research Center not yet accepting patients
    Seattle, Washington, 98109, USA
  • Chris O'Brien Lifehouse accepting new patients
    Camperdown, New South Wales, 2050, Australia
  • Metro South Hospital and Health Service via Princess Alexandra Hospital not yet accepting patients
    Woolloongabba, QLD 4102, Australia
  • Institut Jules Bordet Medical Oncology Clinic accepting new patients
    Brussels, 1000, Belgium
  • University Hospital Leuven accepting new patients
    Leuven, 3000, Belgium
  • Alberta Health Services accepting new patients
    Edmonton, Alberta, T6G 1Z2, Canada
  • Princess Margaret Hospital accepting new patients
    Toronto, Ontario, M5G 1X8, Canada
  • McGill University Health Centre - Royal Victoria Hospital accepting new patients
    Montreal, Quebec, H4A 3J1, Canada
  • Institut Bergonie accepting new patients
    Bordeaux, 33076, France
  • Centre Leon Berard accepting new patients
    Lyon, 69008, France
  • Hospital Pitie Salpetriere accepting new patients
    Paris Cedex 13, 75651, France
  • Institut Curie accepting new patients
    Paris, 75248, France
  • Institut Gustave Roussy accepting new patients
    Villejuif, 94800, France
  • Children's Hospital Augsburg Klinikum accepting new patients
    Augsburg, 86156, Germany
  • Sarcoma Center HELIOS Klinikum Berlin accepting new patients
    Berlin, 13125, Germany
  • Instituto Nazionale Tumori - National Cancer Institute Via Giacomo Venezian accepting new patients
    Milano, 20133, Italy
  • National Taiwan University Hospital accepting new patients
    Taipei City, 10002, Taiwan
  • London Sarcoma Service Department of Oncology accepting new patients
    London, NW1 2PG, United Kingdom
  • Royal Marsden Foundation Trust accepting new patients
    London, SW3 6JJ, United Kingdom

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Epizyme, Inc.
ID
NCT02601950
Phase
Phase 2
Lead Scientist
Thierry Jahan
Study Type
Interventional
Last Updated
January 2017
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