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Advanced Soft-tissue SarcomaPhase 1NCT04204941

Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma

A Phase 1 study testing Tazemetostat and Doxorubicin HCl in people with Advanced Soft-tissue Sarcoma and Advanced Epithelioid Sarcoma, run by Epizyme, Inc. at 21 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The participants of this study will have advanced epithelioid sarcoma. Sarcoma is a cancer of the connective tissues, such as nerves, muscles and bones. Epithelioid sarcoma is an ultra-rare sarcoma of the soft-tissue. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tazemetostat and Doxorubicin HCl
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
21 sitesin 4 countries
Study dates
19 Dec 2019to 14 Jun 2024
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Participants must meet ALL the following inclusion criteria to be eligible to enroll in this study:
  • Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol. Study related activities will not start until written consent is obtained.
  • Life expectancy ≥ 3 months before enrollment
  • Phase 1b: 18-65 years old histologically confirmed Soft Tissue Sarcoma
  • Phase 3: ≥18 years old with unresectable locally advanced or metastatic Epithelioid Sarcoma and tumor tissue available
  • Have measurable disease
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  • Eastern Cooperative Oncology Group Performance Status (ECOG) performance status of 0, 1, or 2
  • Have adequate hematologic (bone marrow (BM) and coagulation factors), renal and hepatic function as required per protocol
  • Females must not be lactating or pregnant at Screening or Baseline
  • Females must not be pregnant or breast feeding and agree to use highly effective contraception during the clinical trial and for 6 months following the final dose of study
  • Male participants of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception
  • Participants diagnosed with human immunodeficiency virus (HIV) are eligible to participate in the study if their infection is well controlled on anti-retroviral therapy.

Who cannot join

  • Participants meeting any of the following exclusion criteria are NOT eligible to enroll in this study:
  • Prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2).
  • Prior systemic anticancer therapy.
  • Contraindications noted in the doxorubicin label
  • Have any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  • Have prior history of T-cell lymphoblastic lymphoma (T- LBL/)/T-cell acute lymphoblastic leukemia (T-ALL).
Show all 22Show fewer
  • Have 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 study treatment.
  • Have known active central nervous system (CNS) or any leptomeningeal metastasis of primary extracranial tumor.
  • Participants taking medications that are known potent cytochrome P450 3A4 (CYP3A4) inducers/inhibitors (including St. John's Wort)
  • Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from the diet and all foods that contain those fruits from time of enrollment to through the duration of study participation.
  • Major surgery within 4 weeks before the first dose of study treatment. Participants must have recovered from surgery prior to enrollment to this study.
  • Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of study treatment.
  • Have an active infection requiring systemic therapy.
  • Are immunocompromised (ie, has a congenital immunodeficiency).
  • Have known hypersensitivity to any component of tazemetostat or doxorubicin.
  • Cardiovascular impairment as stated in the protocol
  • Have a known active infection with hepatitis B virus (HBV, as measured by positive hepatitis B surface antigen), hepatitis C virus (HCV, as measured by positive hepatitis C antibody).
  • Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the participant's participation in this study OR interfere with their ability to receive study treatment or complete the study.
  • Female participants who are pregnant or breastfeeding.
  • Participants who have undergone a solid organ transplant.
  • Participants with malignancies other than STS (phase 1b) or ES (Phase 3 only).
  • Participants housed in an institution by order of the authorities or courts.

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

United States18 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • University of Colorado Hospital - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

  • Dana Farber Cancer Insititute

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Sarah Cannon Research Institute at HealthONE

    Denver, Colorado, 80218

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

  • Sarah Cannon and HCA Research Institute

    Nashville, Tennessee, 37203

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center - Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

  • Fred Hutchinson Research Center

    Seattle, Washington, 98109

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Canada1 site

  • McGill University Faculty of Medicine - Royal Victoria Hospital

    Montreal, Quebec, H4A 3J1

Other trials in Canada

Taiwan1 site

  • National Taiwan University Hospital

    Taipei, 100

Other trials in Taiwan

United Kingdom1 site

  • Royal Marsden Foundation Trust

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: A Phase 1b/3 Global, Randomized, Double-blind, Placebo-Controlled Trial of Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma

The participants of this study will have advanced epithelioid sarcoma. Sarcoma is a cancer of the connective tissues, such as nerves, muscles and bones. Epithelioid sarcoma is an ultra-rare sarcoma of the soft-tissue.

Part 1 of this trial will evaluate the safety and the level of the study drug that the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for the next part of the study.

Read more

Part 2 will evaluate and compare for each of the study drug combinations how long participants live without their disease getting worse.

The study drug is called tazemetostat. The study will test tazemetostat in combination with doxorubicin compared to placebo (dummy treatment) in combination with doxorubicin. Doxorubicin is a current front line treatment for epithelioid sarcoma

Read the detailed description

The open-label phase 1b portion is designed to evaluate the safety of the combination of tazemetostat + doxorubicin, as well as to establish the maximum tolerated dose (MTD) and the Recommended Phase 3 Dose (RP3D). The phase 3 portion of the clinical trial aims to compare tazemetostat + doxorubicin to the current front-line standard treatment, single-agent doxorubicin + placebo, when used as first-line treatment in locally advanced unresectable or metastatic Epithelioid Sarcoma (ES).

The Phase 3 portion was planned but never initiated due to early termination during Phase 1b. Participants with confirmed Soft-tissue Sarcoma (STS) were enrolled in phases 1b.

Being tested
Tazemetostat, Doxorubicin HCl

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TazemetostatDrug

    Also called EPZ-6438, IPN60200

    400 mg, 600 to 800 mg of Tazemetostat will be administered twice daily.

  • Doxorubicin HClDrug

    75mg/m2 intravenous injection day 1 of each cycle for up to 6 cycles

Study groups in NCT04204941
Study groupRoleWhat they receive
Phase 1b: Open-label: Tazemetostat + DoxorubicinExperimentalPhase 1b: On cycle 1 day -1, participants will receive a single morning dose of tazemetostat at the assigned dose level. Participants will receive doxorubicin 75 mg/m2 intravenously (IV) on day 1 of each cycle for up to 6 cycles. Tazemetostat will be escalated from a starting dose of 400 mg twice daily PO to 600 mg twice daily PO to 800 mg twice daily.
Receives: Drug: Tazemetostat; Drug: Doxorubicin HCl

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities (DLTs)

    Determined by Adverse Events (AEs) and clinical laboratory tests.

    Measured: 1 Cycle/21 days

  2. Progression free survival (PFS)

    Phase 3: Assessed by Independent Review Committee. Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints

    Measured: Through study completion, an average of two years.

Secondary outcomes (17)

  1. Phase 1b: Pharmacokinetics (PK) of tazemetostat when administered in combination with doxorubicin in participants with soft tissue sarcoma (STS): Area under the Plasma Concentration Time Curve from time 0 to 24 hours (AUC0-24)

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  2. Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in participants with STS: Area under the Plasma Concentration Time Curve From time 0 to the last observable concentration (AUC0- last)

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  3. Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in Participants with STS: The maximum observed concentration (Cmax).

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  4. Phase 3: Overall Survival (OS)

    Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints

    Measured: Through study completion, an average of two years.

  5. Phase 3: Incidence of Adverse Events (AEs)

    All AEs, including clinically significant laboratory parameters will be graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE). Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints

    Measured: Through study completion, an average of two years.

  6. Phase 3: PFS

    Assessed by the investigator. Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints

    Measured: Through study completion, an average of two years.

  7. Disease control rate (DCR)

    Defined as the number of participants who achieve response complete response (CR) + partial response (PR) or who have stable disease (SD). Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints.

    Measured: Through study completion, an average of two years

  8. Objective response rate (ORR)

    ORR is defined as the proportion of participants achieving complete or partial response. Determined based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    Measured: Through study completion, an average of two years

  9. Duration of treatment (DOR)

    Defined as the time from first documented evidence of CR or PR to the time of first documented disease progression or death, whichever occurs first

    Measured: Through study completion, an average of two years

  10. Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQC) (EORTC QLQC-30)

    The EORTC QLQC-30 physical function, role function, and global health status domains will be assessed

    Measured: Through study completion, an average of two years

  11. Progression-Free Survival on Next Line of Therapy (PFS2)

    Defined as time from randomization to objective tumor progression on next-line treatment or death, whichever occurs first

    Measured: Through study completion, an average of two years

  12. Time to first subsequent anti-cancer therapy ((TFST)

    Defined as the time from randomization to the time to first subsequent therapy

    Measured: Through study completion, an average of two years

  13. Population PK parameters of tazemetostat when administered in combination with doxorubicin: Oral clearance (CL/F)

    CL/F is defined as the apparent oral clearance following administration of tazemetostat when administered in combination with doxorubicin

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  14. Population PK parameters of tazemetostat when administered in combination with doxorubicin: oral volume of distribution (Vss).

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  15. Population PK parameters of tazemetostat when administered in combination with doxorubicin: Area Under the Curve at steady state (AUCss)

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  16. Population PK parameters of tazemetostat when administered in combination with doxorubicin: trough concentration (Ctrough)

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

  17. Population PK parameters of tazemetostat when administered in combination with doxorubicin: Cmax

    Measured: Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2019
  2. Study start19 Dec 2019
  3. Primary completion14 Jun 2024
  4. Study completion14 Jun 2024

Why it stopped: FDA and Ipsen alignelment: Due to unfeasibility and the resulting inability to meet the required enrolment targets. No safety concerns

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04204941
Sponsor's protocol ID
EZH-301
Other IDs
2019-003648-55, 2019
Status last verified
Jan 2026
First submitted
11 Dec 2019
Last updated
7 Jan 2026
Results posted
No
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.

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tazemetostat and Doxorubicin HCl in people with Advanced Soft-tissue Sarcoma and Advanced Epithelioid Sarcoma, run by Epizyme, Inc. at 21 sites in 4 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 12 inclusion and 22 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: stopped early, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Canada, Taiwan, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: FDA and Ipsen alignelment: Due to unfeasibility and the resulting inability to meet the required enrolment targets. No safety concerns). Results are not available in the source record.

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?

Dose Limiting Toxicities (DLTs) (time frame: 1 Cycle/21 days). The study lists 2 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 NCT04204941, 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 7 Jan 2026.

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