Using tazemetostat with doxorubicin for advanced epithelioid sarcoma treatment

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

This study is testing if a new combination of tazemetostat and doxorubicin can safely help people with advanced epithelioid sarcoma live longer compared to just doxorubicin with a placebo.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 164 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ipsen (Industry-sponsored)
• Drugs / interventions: doxorubicin
• Locations: 21 sites (Duarte, California and 20 other locations)
• Trial ID: NCT04204941 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of tazemetostat in combination with doxorubicin as a first-line treatment for patients with advanced epithelioid sarcoma, a rare type of soft-tissue cancer. The study is divided into two parts: the first part assesses the tolerability and establishes the recommended dosage of the drug combination, while the second part compares the survival outcomes of patients receiving the combination therapy against those receiving doxorubicin with a placebo. Participants must have measurable disease and meet specific eligibility criteria to enroll.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable locally advanced or metastatic epithelioid sarcoma.

Not a fit: Patients with other types of sarcoma or those who are not eligible due to health conditions or performance status may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with advanced epithelioid sarcoma.

How similar studies have performed: While the combination of tazemetostat and doxorubicin is being tested in this trial, similar approaches have shown promise in other studies involving targeted therapies for sarcomas.

Eligibility 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. 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-cell acute lymphoblastic leukemia (T- LBL/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 (CYP)3A4 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.

Where this trial is running

Duarte, California and 20 other locations

• City of Hope Comprehensive Cancer Center — Duarte, California, United States (Completed)
• Sarcoma Oncology Research Center — Santa Monica, California, United States (Recruiting)
• University of Colorado Hospital - Anschutz Cancer Pavilion — Aurora, Colorado, United States (Completed)
• Sarah Cannon Research Institute at HealthONE — Denver, Colorado, United States (Completed)
• Mayo Clinic-Jacksonville — Jacksonville, Florida, United States (Completed)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Completed)
• Dana Farber Cancer Insititute — Boston, Massachusetts, United States (Completed)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Completed)
• University of Michigan Medical Center — Ann Arbor, Michigan, United States (Completed)
• Washington University — Saint Louis, Missouri, United States (Completed)
• Columbia University Irving Medical Center — New York, New York, United States (Completed)
• Duke University Medical Center — Durham, North Carolina, United States (Completed)
• The Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (Recruiting)
• Oregon Health and Science University — Portland, Oregon, United States (Completed)
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (Completed)
• University of Pittsburgh Medical Center - Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Completed)
• Sarah Cannon and HCA Research Institute — Nashville, Tennessee, United States (Completed)
• Fred Hutchinson Research Center — Seattle, Washington, United States (Completed)
• McGill University Faculty of Medicine - Royal Victoria Hospital — Montréal, Quebec, Canada (Completed)
• National Taiwan University Hospital — Taipei, Taiwan (Completed)
• Royal Marsden Foundation Trust — London, United Kingdom (Completed)

Study contacts

• Study coordinator: Ipsen Clinical Study Enquiries

Conditions Advanced Soft-tissue Sarcoma; Advanced Epithelioid Sarcoma