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

NCT ID: NCT04204941

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-19
• Study Completion Date: 2024-06-14

Brief 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.

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.

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

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.

Conditions

Advanced Soft-tissue Sarcoma; Advanced Epithelioid Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tazemetostat

Intervention Type: DRUG

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

Doxorubicin HCl

Intervention Type: DRUG

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

Interventions

Tazemetostat

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

Intervention Type: DRUG

Doxorubicin HCl

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

Intervention Type: DRUG

Other Intervention Names

EPZ-6438; IPN60200

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Epizyme, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Sarcoma Oncology Research Center

Santa Monica, California, United States

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Insititute

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Washington University

St Louis, Missouri, United States

Columbia University Irving Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Fred Hutchinson Research Center

Seattle, Washington, United States

McGill University Faculty of Medicine - Royal Victoria Hospital

Montreal, Quebec, Canada

National Taiwan University Hospital

Taipei, , Taiwan

Royal Marsden Foundation Trust

London, , United Kingdom

Countries

United States; Canada; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33035459 (View on PubMed)

Other Identifiers

2019-003648-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EZH-301

Identifier Type: -

Identifier Source: org_study_id