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

NCT04204941 | Terminated Phase 1 FDA Drug

• 2 other identifiers: EZH-3012019-003648-55
• Study Type: interventional
• Target: 25
• Locations: 4 countries
• Sites: 21

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

Conditions

Advanced Soft-tissue Sarcoma; Advanced Epithelioid Sarcoma

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLTs)

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

  1 Cycle/21 days

• 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

  Through study completion, an average of two years.

Secondary Outcomes (17)

• 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)

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

• 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)

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

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

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

• Phase 3: Overall Survival (OS)

  Through study completion, an average of two years.

• Phase 3: Incidence of Adverse Events (AEs)

  Through study completion, an average of two years.

Study Arms (1)

Phase 1b: Open-label: Tazemetostat + Doxorubicin

EXPERIMENTAL

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; Drug: Doxorubicin HCl

Interventions

Tazemetostat DRUG

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

Also known as: EPZ-6438, IPN60200

Phase 1b: Open-label: Tazemetostat + Doxorubicin

Doxorubicin HCl DRUG

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

Phase 1b: Open-label: Tazemetostat + Doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Epizyme, Inc.: lead

Study Sites (21)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Insititute

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, 37203, United States

Location

Fred Hutchinson Research Center

Seattle, Washington, 98109, United States

Location

McGill University Faculty of Medicine - Royal Victoria Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Royal Marsden Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33035459 DERIVED

MeSH Terms

Interventions

tazemetostat; Doxorubicin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 19, 2019
• Study Start: December 19, 2019
• Primary Completion: June 14, 2024
• Study Completion: June 14, 2024
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the United States (US) and/or Europe (EU).
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

GB (1); TW (1); US (18); CA (1)