Malignant Rhabdoid Tumors (MRT)Phase 2NCT02601950
A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
A Phase 2 study testing Tazemetostat in people with Malignant Rhabdoid Tumors (MRT) and Rhabdoid Tumors of the Kidney (RTK), run by Epizyme, Inc. at 32 sites in 9 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Rhabdoid Tumors (MRT), Rhabdoid Tumors of the Kidney (RTK), Atypical Teratoid Rhabdoid Tumors (ATRT)
- What is being tested?
- Tazemetostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 267 participants
- Where
- 32 sitesin 9 countries
- Study dates
- 22 Dec 2015to 26 Feb 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors
- Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function.
- For subjects with CNS Tumors 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
- 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
- Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec
- Female subjects of childbearing potential must:
- Have a negative beta-human chorionic gonadotropin (β-hCG) pregnancy test at time of screening and within 14 days prior to planned first dose of tazemetostat and
- Agree to use effective contraception from a minimum of 7 days prior to first dose until 6 months following the last dose of tazemetostat and have a male partner who uses a condom, or
- Practice true abstinence or have a male partner who is vasectomized
- Male subjects with a female partner of childbearing potential must:
- Be vasectomized, or
- Agree to use condoms as defined in Section 8.6.2, from first dose of tazemetostat until 3 months following the last dose of tazemetostat, or
- Have a female partner who is NOT of childbearing potential
Who cannot join
- 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.
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- 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.
Trial locations and contacts
32 sites in 9 countries.
32 sites in 9 countries
United States14 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Denver
Aurora, Colorado, 80045
Massachusetts General Hospital - Cancer Center
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Oregon Health Sciences University
Portland, Oregon, 97239
University of California San Francisco
San Francisco, California, 94115
Seattle Children's Hospital
Seattle, Washington, 98105
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Washington University
St Louis, Missouri, 63130
France5 sites
Institut Bergonie
Bordeaux, 33076
Centre Leon Berard
Lyon, 69008
Institut Curie
Paris, 75248
Hospital Pitie Salpetriere
Paris, 75651
Institut Gustave Roussy
Villejuif, 94800
Canada3 sites
Alberta Health Services
Edmonton, Alberta, T6G 1Z2
McGill University Health Centre - Royal Victoria Hospital
Montreal, Quebec, H4A 3J1
Princess Margaret Hospital
Toronto, Ontario, M5G 1X8
Australia2 sites
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Metro South Hospital and Health Service via Princess Alexandra Hospital
Woolloongabba, QLD 4102
Belgium2 sites
Institut Jules Bordet Medical Oncology Clinic
Brussels, 1000
University Hospital Leuven
Leuven, 3000
Germany2 sites
Children's Hospital Augsburg Klinikum
Augsburg, 86156
Sarcoma Center HELIOS Klinikum Berlin
Berlin, 13125
United Kingdom2 sites
University College London Hospital
London, NW1 2PG
Royal Marsden Foundation Trust
London, SW3 6JJ
Italy1 site
Instituto Nazionale Tumori - National Cancer Institute Via Giacomo Venezian
Milan, 20133
About this study
Official title: A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma
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.
Read more
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).
Read the detailed description
This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID (twice daily) and 1600 mg QD (once daily). Subjects will be screened for eligibility within 21 days of the planned date of the first dose of tazemetostat and enrolled into one of 8 cohorts:
Cohort using tazemetostat 800 mg BID
- Cohort 1 (Closed for enrollment): malignant rhabdoid tumor (MRT), rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and 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 (Closed for enrollment): Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement
- Cohort 3 (Closed for enrollment): Other integrase interactor 1 (INI1) negative tumors or any solid tumor with an enhancer of zeste homologue-2 (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 (Closed for enrollment): Renal medullary carcinoma (RMC)
- Cohort 5 (Closed for enrollment): Epithelioid sarcoma (ES)
- Cohort 6 (Closed for enrollment): Epithelioid sarcoma (ES) undergoing mandatory tumor biopsy
- Cohort 7 (Closed for enrollment): Poorly differentiated chordoma (or other chordoma with Sponsor approval)
Cohort using tazemetostat 1600 mg QD
- Cohort 8 (Closed for enrollment): Epitheliod sarcoma
Participants will be dosed in continuous 28-day cycles. (Note: if treatment with study drug is discontinued prior to completing 2 years, subjects will be followed for a maximum duration of 2 years from start of study drug dosing.) Response assessment will be performed every 8 weeks while on study.
Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study.
- Conditions
- 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
- Being tested
- Tazemetostat
- Medical subject headings
- Sarcoma, Synovial, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TazemetostatDrug
Also called EPZ-6438, E7438, IPN60200
Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
| Study group | Role | What they receive |
|---|---|---|
| Open-label Tazemetostat | Experimental | All cohorts will receive 800 mg oral Tazemetostat twice a day in continuous 28-day cycles. Receives: Drug: Tazemetostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohorts 1, 3, 4, 5, 6 and 7: Objective Response Rate (ORR)
ORR was defined as percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) based on the investigator review from start of treatment until progressive disease (PD) or start of subsequent anti-cancer therapy or cancer-related surgery, whichever was earlier, as per response assessment in neuro-oncology (RANO) criteria for primary brain tumors or response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria for all other solid tumors. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in short axis. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since treatment started. In addition, sum must have an absolute increase from nadir of 5 mm.
Measured: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)
Cohort 2: Progression-Free Survival (PFS) Rate at 16 Weeks of Treatment With Tazemetostat
PFS was defined as the interval of time between the date of the first dose of study treatment and the earliest date of PD or death due to any cause, whichever comes first, as per RECIST v 1.1 criteria. PFS rate at 16 week was estimated. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm.
Measured: At 16 Weeks
Cohort 8: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was medically significant. TEAEs were defined as AEs if one of the following conditions met: emerged after the time of first dose administration, having been absent prior to the first dose; re-emerged, having been present but stopped prior to the time of first dose administration; worsened in severity after the time of first dose administration relative to the pretreatment state, when the AE was continuous.
Measured: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 148 weeks
Secondary outcomes (7)
All Cohorts: Duration of Response (DOR)
DOR was defined as time from the first documented evidence of CR or PR based on investigator review to the time of first documented PD or death due to any cause, whichever came first, as per RECIST v 1.1 criteria. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm.
Measured: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration 28 days)
All Cohorts: Progression-Free Survival (PFS)
PFS was defined as the interval of time between the date of the first dose of study treatment and the earliest date of PD or death due to any cause, whichever comes first, as per RECIST v 1.1 criteria. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm.
Measured: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration 28 days)
All Cohorts: Progression-Free Survival (PFS) Rate at Weeks 24, 32 and 56
PFS was defined as the interval of time between the date of the first dose of study treatment and the earliest date of PD or death due to any cause, whichever comes first, as per RECIST v 1.1 criteria. PFS rate at 24, 32 and 56 weeks were estimated. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm. Estimates were calculated with Kaplan-Meier analysis and 95% CIs using the complementary log-log transformation.
Measured: At Weeks 24, 32 and 56
All Cohorts: Overall Survival (OS)
OS was defined as the interval of time between the date of the first dose of study treatment and the date of death due to any cause.
Measured: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)
All Cohorts: Overall Survival (OS) Rate at Weeks 24, 32 and 56
OS was defined as the interval of time between the date of the first dose of study treatment and the date of death due to any cause. OS rate at 24, 32 and 56 weeks were estimated. Estimates were calculated with Kaplan-Meier analysis and 95% CIs using the complementary log-log transformation.
Measured: At Weeks 24, 32 and 56
All Cohorts: Disease Control Rate (DCR) at Weeks 12, 24, 32 and 48
DCR was defined as the percentage of participants who achieved a confirmed response (CR or PR, as per RECIST v 1.1 criteria) or who have SD lasting at least 32 weeks from the start of treatment until disease progression or the start of subsequent anti-cancer therapy. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. SD was defined neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Measured: At Weeks 12, 24, 32 and 48
Cohorts 2 and 8: Objective Response Rate (ORR)
ORR was defined as percentage of participants who achieved a confirmed CR or PR based on investigator assessment from start of treatment until PD or start of subsequent anti-cancer therapy or cancer-related surgery, whichever was earlier, as per RANO criteria for primary brain tumors or RECIST v 1.1 criteria for all other solid tumors. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm.
Measured: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2015 (estimated)
- Study start22 Dec 2015
- Primary completion26 Feb 2024
- Study completion26 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant Rhabdoid Tumors (MRT)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epizyme, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02601950
- Sponsor's protocol ID
- EZH-202
- Other IDs
- 2015-002469-41, 2015
- Status last verified
- Jun 2025
- First submitted
- 21 Oct 2015
- Last updated
- 22 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
Publications
Gounder M, Schoffski P, Jones RL, Agulnik M, Cote GM, Villalobos VM, Attia S, Chugh R, Chen TW, Jahan T, Loggers ET, Gupta A, Italiano A, Demetri GD, Ratan R, Davis LE, Mir O, Dileo P, Van Tine BA, Pressey JG, Lingaraj T, Rajarethinam A, Sierra L, Agarwal S, Stacchiotti S. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 2020 Nov;21(11):1423-1432. doi: 10.1016/S1470-2045(20)30451-4. Epub 2020 Oct 6.
PubMed 33035459
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma
- ClinicalTrials.gov ID
- NCT02601950
- Acronym / sponsor ID
- EZH-202
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 267 participants (actual)
- Lead sponsor
- Epizyme, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Dec 2015 (actual)
- Primary completion
- 26 Feb 2024 (actual)
- Study completion
- 26 Feb 2024 (actual)
- First posted
- 11 Nov 2015 (estimated)
- Results
- Posted 11 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID (twice daily) and 1600 mg QD (once daily). Subjects will be screened for eligibility within 21 days of the planned date of the first dose of tazemetostat and enrolled into one of 8 cohorts:
Cohort using tazemetostat 800 mg BID
- Cohort 1 (Closed for enrollment): malignant rhabdoid tumor (MRT), rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and 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 (Closed for enrollment): Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement
- Cohort 3 (Closed for enrollment): Other integrase interactor 1 (INI1) negative tumors or any solid tumor with an enhancer of zeste homologue-2 (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 (Closed for enrollment): Renal medullary carcinoma (RMC)
- Cohort 5 (Closed for enrollment): Epithelioid sarcoma (ES)
- Cohort 6 (Closed for enrollment): Epithelioid sarcoma (ES) undergoing mandatory tumor biopsy
- Cohort 7 (Closed for enrollment): Poorly differentiated chordoma (or other chordoma with Sponsor approval)
Cohort using tazemetostat 1600 mg QD
- Cohort 8 (Closed for enrollment): Epitheliod sarcoma
Participants will be dosed in continuous 28-day cycles. (Note: if treatment with study drug is discontinued prior to completing 2 years, subjects will be followed for a maximum duration of 2 years from start of study drug dosing.) Response assessment will be performed every 8 weeks while on study.
Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-label Tazemetostat | Experimental | Drug: TazemetostatAll cohorts will receive 800 mg oral Tazemetostat twice a day in continuous 28-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- 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:
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TazemetostatAlso: EPZ-6438, E7438, IPN60200Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 gene | Drug | Open-label Tazemetostat |
Primary outcome
Cohorts 1, 3, 4, 5, 6 and 7: Objective Response Rate (ORR)
Time frame: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)
ORR was defined as percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) based on the investigator review from start of treatment until progressive disease (PD) or start of subsequent anti-cancer therapy or cancer-related surgery, whichever was earlier, as per response assessment in neuro-oncology (RANO) criteria for primary brain tumors or response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria for all other solid tumors. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in short axis. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since treatment started. In addition, sum must have an absolute increase from nadir of 5 mm.
Cohort 2: Progression-Free Survival (PFS) Rate at 16 Weeks of Treatment With Tazemetostat
Time frame: At 16 Weeks
PFS was defined as the interval of time between the date of the first dose of study treatment and the earliest date of PD or death due to any cause, whichever comes first, as per RECIST v 1.1 criteria. PFS rate at 16 week was estimated. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm.
Cohort 8: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 148 weeks
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was medically significant. TEAEs were defined as AEs if one of the following conditions met: emerged after the time of first dose administration, having been absent prior to the first dose; re-emerged, having been present but stopped prior to the time of first dose administration; worsened in severity after the time of first dose administration relative to the pretreatment state, when the AE was continuous.
7 secondary outcomes
All Cohorts: Duration of Response (DOR)
Time frame: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration 28 days)
All Cohorts: Progression-Free Survival (PFS)
Time frame: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration 28 days)
All Cohorts: Progression-Free Survival (PFS) Rate at Weeks 24, 32 and 56
Time frame: At Weeks 24, 32 and 56
All Cohorts: Overall Survival (OS)
Time frame: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)
All Cohorts: Overall Survival (OS) Rate at Weeks 24, 32 and 56
Time frame: At Weeks 24, 32 and 56
All Cohorts: Disease Control Rate (DCR) at Weeks 12, 24, 32 and 48
Time frame: At Weeks 12, 24, 32 and 48
Cohorts 2 and 8: Objective Response Rate (ORR)
Time frame: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33035459Gounder M, Schoffski P, Jones RL, Agulnik M, Cote GM, Villalobos VM, Attia S, Chugh R, Chen TW, Jahan T, Loggers ET, Gupta A, Italiano A, Demetri GD, Ratan R, Davis LE, Mir O, Dileo P, Van Tine BA, Pressey JG, Lingaraj T, Rajarethinam A, Sierra L, Agarwal S, Stacchiotti S. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 2020 Nov;21(11):1423-1432. doi: 10.1016/S1470-2045(20)30451-4. Epub 2020 Oct 6.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ipsen Medical Director study director
Ipsen
32 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tazemetostat in people with Malignant Rhabdoid Tumors (MRT) and Rhabdoid Tumors of the Kidney (RTK), run by Epizyme, Inc. at 32 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 38 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, France, Canada, Australia, Belgium and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohorts 1, 3, 4, 5, 6 and 7: Objective Response Rate (ORR) (time frame: Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02601950, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.