A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma

Completed · Phase 2

Conditions studied: 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, Poorly Differentiated Chordoma (or Other Chordoma With Sponsor Approval), Any Solid Tumor With an EZH2 GOF Mutation

In brief

This study will include participants with various types of cancer known as soft-tissue sarcomas. Tissues that can be affected by soft tissue sarcomas include fat, muscle, blood vessels, deep skin tissues, tendons and ligaments. Soft tissue cancers are rare and can occur almost anywhere in the body. Part 1 of this trial will study the safety and the level that adverse effects of the study drug tazemetostat in combination with doxorubicin (current front line treatment) can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for the next part of the study. Part 2 will evaluate and compare how long participants live without their disease getting worse when receiving the study drug plus doxorubicin versus doxorubicin plus placebo (dummy treatment).

Key facts

Study ID: NCT02601950
Run by: Epizyme, Inc.
People needed: 267
Starts: 2015-12-22
Expected to finish: 2024-02-26
Last updated by the study team: 2025-06-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age (at the time of consent/assent): ≥18 years of age
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Has provided signed written informed consent
Has a life expectancy of >3 months
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, Cohort 6 and Cohort 8 ONLY)
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
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
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)
For Cohort 3, 4, 5, 7 and 8 (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
For Cohort 6 (subjects with ES undergoing optional tumor biopsy) only:
Morphology and immunophenotypic panel consistent with ES (e.g., CD34, EMA, Keratin, and INI1)
Has all prior treatment (i.e. chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤Grade 1 per CTCAE version 4.0.3 or are clinically stable and not clinically significant, at time of enrollment.
Prior anti-cancer therapy(ies), if applicable, must be completed according to the criteria below:
Chemotherapy: cytotoxic (At least 14 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 28 days 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)
Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing

You may not qualify if…

Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
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
Has known active CNS or any leptomeningeal metastasis of primary extra-cranial tumor.
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
Has had major surgery within 3 weeks prior to enrollment
Has Thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and MPN (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
Has a prior history of T-LBL /T-ALL
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
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
Is currently taking any prohibited medication(s)
Has an active infection requiring systemic treatment
Is immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV)
Has known active infection with hepatitis B virus or hepatitis C virus
Has had a symptomatic venous thrombosis within 2 weeks prior to study enrollment -
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
Has known hypersensitivity to any of the component of tazemetostat or other inhibitor(s)of EZH2
Is unable to take oral medications, or has a malabsorption syndrome or any uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that would limit compliance with study requirements.
Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.
For female subjects of childbearing potential: Is pregnant or nursing
For male subjects: Is unwilling to adhere to contraception criteria from time of enrollment in the study to at least 3 months after last dose of tazemetostat.

Where it is running

University of California San Francisco — San Francisco, California, United States
University of Colorado Denver — Aurora, Colorado, United States
Mayo Clinic - Jacksonville — Jacksonville, Florida, United States
Northwestern Memorial Hospital — Chicago, Illinois, United States
Massachusetts General Hospital - Cancer Center — Boston, Massachusetts, United States
Dana Farber Cancer Institute — Boston, Massachusetts, United States
University of Michigan — Ann Arbor, Michigan, United States
Washington University — St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center — New York, New York, United States
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
Oregon Health Sciences University — Portland, Oregon, United States
MD Anderson Cancer Center — Houston, Texas, United States
Seattle Children's Hospital — Seattle, Washington, United States
Fred Hutchinson Cancer Research Center — Seattle, Washington, United States
Chris O'Brien Lifehouse — Camperdown, New South Wales, Australia
Metro South Hospital and Health Service via Princess Alexandra Hospital — Woolloongabba, Australia
Institut Jules Bordet Medical Oncology Clinic — Brussels, Belgium
University Hospital Leuven — Leuven, Belgium
Alberta Health Services — Edmonton, Alberta, Canada
Princess Margaret Hospital — Toronto, Ontario, Canada
McGill University Health Centre - Royal Victoria Hospital — Montreal, Quebec, Canada
Institut Bergonie — Bordeaux, France
Centre Leon Berard — Lyon, France
Institut Curie — Paris, France
Hospital Pitie Salpetriere — Paris, France

Full record on ClinicalTrials.gov

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