Clinical Trials /

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

NCT04204941

Description:

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.

Related Conditions:
  • Epithelioid Sarcoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: EZH-301
  • NCT ID: NCT04204941

Conditions

  • Advanced Soft Tissue Sarcoma
  • Advanced Epithelioid Sarcoma

Interventions

DrugSynonymsArms
TazemetostatEPZ-6438Tazemetostat + Doxorubicin Arm
PlaceboPlacebo + Doxorubicin Arm
Doxorubicin HClPlacebo + Doxorubicin Arm

Purpose

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.

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
      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 ES.
    

Trial Arms

NameTypeDescriptionInterventions
Tazemetostat + Doxorubicin ArmExperimentalTazemetostat 800 mg (or RP3D from the phase 1b) administered orally twice daily in continuous 21-day cycles. Doxorubicin 75 mg/m2 intravenously (IV) on day 1 cycle 1 then on day 1 of cycles 2-6.
  • Tazemetostat
  • Doxorubicin HCl
Placebo + Doxorubicin ArmExperimentalPlacebo administered orally twice daily in continuous 21-day cycles. Doxorubicin 75 mg/m2 IV on day 1 of cycle 1 then day 1 of cycles 2-6.
  • Placebo
  • Doxorubicin HCl

Eligibility 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.

          2. Phase 1b: 18-35 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 while on
             study.

          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. Venous thrombosis or pulmonary embolism within the last 1 month before starting 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. 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).

         16. 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.

         17. Subjects who have undergone a solid organ transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:DLT's as determined by Adverse Events following administration of Tazemostat in Combination with Doxorubicin
Time Frame:1 Cycle/21 days
Safety Issue:
Description:Phase 1b: Evaluate the safety and tolerability of tazmetostat in combination with doxorubicin in subjects with advanced STS and select a dose for further evaluation in phase 3 (the RP3D) Phase 3: Evaluate and compare the PFS by independent review committee in subjects with advanced ES treated with tazmetostat + doxorubicin versus placebo + doxorubicin

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Epizyme, Inc.

Last Updated

December 24, 2020