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

• Status: Recruiting
• Trial end date: 2029-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, double-blind, placebo-controlled, randomized phase 3 study with phase 1b portion designed to establish a recommended phase 3 dose (RP3D) and to evaluate the efficacy, PK, and safety of tazemetostat + doxorubicin vs placebo + doxorubicin in subjects with advanced epithelioid sarcoma (ES). This study will be conducted in 2 parts.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Epizyme, Inc.
• Treatments: Doxorubicin; Liposomal doxorubicin

Criteria

Inclusion Criteria

Subjects 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. Phase 1b: 18-65 years old histologically confirmed STS

3. Phase 3: ≥18 years old with Epithelioid Sarcoma

4. Have measurable disease

5. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative pregnancy test)

6. Because of unknown impact on a developing fetus, 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

7. Male subjects of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception and use a condom throughout the study period and for 3 months after doxorubicin or tazmetostat discontinuation.

8. Subjects 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

Subjects 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. Have any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

4. Have prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia (T- LBL/T-ALL).

5. 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.

6. Have known active central nervous system (CNS) or any leptomeningeal metastasis of primary extracranial tumor.

7. Subjects taking medications that are known potent cytochrome P450 (CYP)3A4 inducers/inhibitors (including St. John's Wort)

8. 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.

9. Major surgery within 4 weeks before the first dose of study treatment. Subjects must have recovered from surgery prior to enrollment to this study.

10. 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.

11. Have an active infection requiring systemic therapy.

12. Are immunocompromised (ie, has a congenital immunodeficiency).

13. Have known hypersensitivity to any component of tazemetostat or doxorubicin.

14. 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).

15. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.

16. Female subjects who are pregnant or breastfeeding.

17. Subjects who have undergone a solid organ transplant.

18. Subjects housed in an institution by order of the authorities or courts.