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

Sponsor
Epizyme, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04204941
Collaborator
(none)
164
Enrollment
21
Locations
2
Arms
112.4
Anticipated Duration (Months)
7.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
164 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
Phase 1b is open label, phase 3 is not open label
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 19, 2019
Anticipated Primary Completion Date :
Mar 15, 2027
Anticipated Study Completion Date :
May 1, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tazemetostat + Doxorubicin Arm

Tazemetostat (800 mg) administered orally twice daily in continuous 21-day cycles during cycles 1-6 and in continuous 28-day cycles during cycle 7 and beyond. Doxorubicin 75 mg/m2 IV on day 1 of cycles 1-6.

Drug: Tazemetostat
Tazemetostat will be administered twice daily.
Other Names:
  • EPZ-6438

    • Drug: Doxorubicin HCl
    75mg/m2 intravenous injection day 1 of cycles 1 to 6
    Experimental: Placebo + Doxorubicin Arm

    Placebo administered orally twice daily in continuous 21-day cycles during cycles 1-6 and in continuous 28-day cycles during cycles 7 and beyond. Doxorubicin 75 mg/m2 IV on day 1 of cycles 1-6.

    Drug: Placebo
    Placebo will be administered twice daily.

    Drug: Doxorubicin HCl
    75mg/m2 intravenous injection day 1 of cycles 1 to 6

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicities (DLTs) as determined by Adverse Events following administration of Tazemostat in Combination with Doxorubicin [1 Cycle/21 days]

      Phase 1b: Evaluate the safety and tolerability of tazemetostat in combination with doxorubicin in subjects with advanced soft tissue sarcoma (STS) and select a dose for further evaluation in phase 3 (the RP3D) Phase 3: Evaluate and compare the progression free survival (PFS) by independent review committee in subjects with advanced ES treated with tazmetostat + doxorubicin versus placebo + doxorubicin

    2. Progression free survival (PFS) [through study completion, an average of one year.]

      Phase 3 Evaluate and compare the PFS by independent review committee (IRC) in subjects with advanced ES treated with tazemetostat + doxorubicin versus placebo + doxorubicin through study completion, an average of one year.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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. 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 subjects of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception

    11. 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. 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. Subjects 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. Subjects 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 subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.

    18. Female subjects who are pregnant or breastfeeding.

    19. Subjects who have undergone a solid organ transplant.

    20. Subjects with malignancies other than STS (phase 1b) or ES (Phase 3 only).

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 Sarcoma Oncology Research Center Santa Monica California United States 90403
    3 University of Colorado Hospital - Anschutz Cancer Pavilion Aurora Colorado United States 80045
    4 Sarah Cannon Research Institute at HealthONE Denver Colorado United States 80218
    5 Mayo Clinic-Jacksonville Jacksonville Florida United States 32224
    6 Massachusetts General Hospital Boston Massachusetts United States 02214
    7 Dana Farber Cancer Insititute Boston Massachusetts United States 02215
    8 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    9 University of Michigan Medical Center Ann Arbor Michigan United States 48109
    10 Washington University Saint Louis Missouri United States 63110
    11 Columbia University Irving Medical Center New York New York United States 10032
    12 Duke University Medical Center Durham North Carolina United States 27710
    13 The Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    14 Oregon Health and Science University Portland Oregon United States 97239
    15 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    16 University of Pittsburgh Medical Center - Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    17 Sarah Cannon and HCA Research Institute Nashville Tennessee United States 37203
    18 Fred Hutchinson Research Center Seattle Washington United States 98109
    19 McGill University Faculty of Medicine - Royal Victoria Hospital Montréal Quebec Canada H4A 3J1
    20 National Taiwan University Hospital Taipei Taiwan 100
    21 Royal Marsden Foundation Trust London United Kingdom SW3 6JJ

    Sponsors and Collaborators

    • Epizyme, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Epizyme, Inc.
    ClinicalTrials.gov Identifier:
    NCT04204941
    Other Study ID Numbers:
    • EZH-301
    First Posted:
    Dec 19, 2019
    Last Update Posted:
    Feb 2, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Sarcoma
    Doxorubicin
    Liposomal doxorubicin

    Study Results

    No Results Posted as of Feb 2, 2022