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

Recruitment Status: TERMINATED
(See Contacts and Locations)Verified December 2025 by Epizyme, Inc.
Sponsor: Epizyme, Inc.
Information Provided by (Responsible Party): Epizyme, Inc.

Clinicaltrials.gov Identifier: NCT04204941
Other Study ID Numbers:: EZH-301

First Submitted: December 10, 2019
First Posted: December 18, 2019
Last Update Posted: January 6, 2026
Last Verified: December 2025

ClinicalTrials.gov processed this data on January 2026. Link to the current ClinicalTrials.gov record .

Study Details

Study 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.

Condition or Disease	Intervention/Treatment
Advanced Soft-tissue SarcomaAdvanced Epithelioid Sarcoma	Drug: Tazemetostat

Study Design

Study Type	Interventional
Actual Enrollment	25 participants
Design Allocation	N/A
Interventional Model	Single Group Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
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
Study Start Date	December 18, 2019
Actual Primary Completion Date	June 13, 2024
Actual Study Completion Date	June 13, 2024

Groups and Cohorts

Group/Cohort	Intervention/Treatment
Phase 1b: Open-label: Tazemetostat + Doxorubicin Phase 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.	Drug: Tazemetostat 400 mg, 600 to 800 mg of Tazemetostat will be administered twice daily.

Group/Cohort

Intervention/Treatment

Phase 1b: Open-label: Tazemetostat + Doxorubicin: Phase 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.

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

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicities (DLTs)
Determined by Adverse Events (AEs) and clinical laboratory tests.
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

Secondary Outcome Measures

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)
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)
Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in Participants with STS: The maximum observed concentration (Cmax).
Phase 3: Overall Survival (OS)
Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints
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
Phase 3: PFS
Assessed by the investigator. Phase 3 was planned but never initiated; therefore, no data were collected for these endpoints
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.
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
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
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
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
Time to first subsequent anti-cancer therapy ((TFST)
Defined as the time from randomization to the time to first subsequent therapy
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
Population PK parameters of tazemetostat when administered in combination with doxorubicin: oral volume of distribution (Vss).
Population PK parameters of tazemetostat when administered in combination with doxorubicin: Area Under the Curve at steady state (AUCss)
Population PK parameters of tazemetostat when administered in combination with doxorubicin: trough concentration (Ctrough)
Population PK parameters of tazemetostat when administered in combination with doxorubicin: Cmax

Eligibility Criteria

Ages Eligible for Study	(Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	Inclusion Criteria Participants must meet ALL the following inclusion criteria to be eligible to enroll in this study: 1. 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. 2. Life expectancy ≥ 3 months before enrollment 3. Phase 1b: 18-65 years old histologically confirmed Soft Tissue Sarcoma 4. Phase 3: ≥18 years old with unresectable locally advanced or metastatic Epithelioid Sarcoma and tumor tissue available 5. Have measurable disease 6. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status of 0, 1, or 2 7. Have adequate hematologic (bone marrow (BM) and coagulation factors), renal and hepatic function as required per protocol 8. Females must not be lactating or pregnant at Screening or Baseline 9. 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 10. Male participants of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception 11. Participants diagnosed with human immunodeficiency virus (HIV) are eligible to participate in the study if their infection is well controlled on anti-retroviral therapy.
Exclusion Criteria	Inclusion Criteria Participants must meet ALL the following inclusion criteria to be eligible to enroll in this study: 1. 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. 2. Life expectancy ≥ 3 months before enrollment 3. Phase 1b: 18-65 years old histologically confirmed Soft Tissue Sarcoma 4. Phase 3: ≥18 years old with unresectable locally advanced or metastatic Epithelioid Sarcoma and tumor tissue available 5. Have measurable disease 6. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status of 0, 1, or 2 7. Have adequate hematologic (bone marrow (BM) and coagulation factors), renal and hepatic function as required per protocol 8. Females must not be lactating or pregnant at Screening or Baseline 9. 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 10. Male participants of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception 11. Participants diagnosed with human immunodeficiency virus (HIV) are eligible to participate in the study if their infection is well controlled on anti-retroviral therapy. Exclusion Criteria Participants meeting any of the following exclusion criteria are NOT eligible to enroll in this study: 1. Prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2). 2. Prior systemic anticancer therapy. 3. Contraindications noted in the doxorubicin label 4. Have any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). 5. Have prior history of T-cell lymphoblastic lymphoma (T- LBL/)/T-cell acute lymphoblastic leukemia (T-ALL). 6. 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. 7. Have known active central nervous system (CNS) or any leptomeningeal metastasis of primary extracranial tumor. 8. Participants taking medications that are known potent cytochrome P450 3A4 (CYP3A4) inducers/inhibitors (including St. John's Wort) 9. 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. 10. Major surgery within 4 weeks before the first dose of study treatment. Participants must have recovered from surgery prior to enrollment to this study. 11. 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. 12. Have an active infection requiring systemic therapy. 13. Are immunocompromised (ie, has a congenital immunodeficiency). 14. Have known hypersensitivity to any component of tazemetostat or doxorubicin. 15. Cardiovascular impairment as stated in the protocol 16. 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). 17. 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. 18. Female participants who are pregnant or breastfeeding. 19. Participants who have undergone a solid organ transplant. 20. Participants with malignancies other than STS (phase 1b) or ES (Phase 3 only). 21. Participants housed in an institution by order of the authorities or courts.

Contacts and Locations

Sponsors and Collaborators	Epizyme, Inc.
Locations	City of Hope Comprehensive Cancer Center \| Duarte California, United States, 91010Sarcoma Oncology Research Center \| Santa Monica California, United States, 90403University of Colorado Hospital - Anschutz Cancer Pavilion \| Aurora Colorado, United States, 80045Sarah Cannon Research Institute at HealthONE \| Denver Colorado, United States, 80218Mayo Clinic-Jacksonville \| Jacksonville Florida, United States, 32224Massachusetts General Hospital \| Boston Massachusetts, United States, 02214Dana Farber Cancer Insititute \| Boston Massachusetts, United States, 02215Dana Farber Cancer Institute \| Boston Massachusetts, United States, 02215University of Michigan Medical Center \| Ann Arbor Michigan, United States, 48109Washington University \| St Louis Missouri, United States, 63110Columbia University Irving Medical Center \| New York New York, United States, 10032Duke University Medical Center \| Durham North Carolina, United States, 27710The Ohio State University Comprehensive Cancer Center \| Columbus Ohio, United States, 43210Oregon Health and Science University \| Portland Oregon, United States, 97239Thomas Jefferson University Hospital \| Philadelphia Pennsylvania, United States, 19107University of Pittsburgh Medical Center - Hillman Cancer Center \| Pittsburgh Pennsylvania, United States, 15232Sarah Cannon and HCA Research Institute \| Nashville Tennessee, United States, 37203Fred Hutchinson Research Center \| Seattle Washington, United States, 98109McGill University Faculty of Medicine - Royal Victoria Hospital \| Montreal Quebec, Canada, H4A 3J1National Taiwan University Hospital \| Taipei , Taiwan, 100Royal Marsden Foundation Trust \| London , United Kingdom, SW3 6JJ
Investigators	Study Director: Ipsen Medical Director, Ipsen

More Information

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.