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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04204941
Recruitment Status : Recruiting
First Posted : December 19, 2019
Last Update Posted : February 2, 2022
Sponsor:
Information provided by (Responsible Party):
Epizyme, Inc.

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
Advanced Soft Tissue Sarcoma Advanced Epithelioid Sarcoma Drug: Tazemetostat Drug: Placebo Drug: Doxorubicin HCl Phase 3

Expanded Access : Epizyme, Inc. has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : December 19, 2019
Estimated Primary Completion Date : March 15, 2027
Estimated Study Completion Date : May 1, 2029


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 Name: 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




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) as determined by Adverse Events following administration of Tazemostat in Combination with Doxorubicin [ Time Frame: 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) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04204941


Contacts
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Contact: Medical Affairs +1 (855) 500-1011 clinicaltrials@epizyme.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Epizyme, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Epizyme, Inc.
ClinicalTrials.gov Identifier: NCT04204941    
Other Study ID Numbers: EZH-301
First Posted: December 19, 2019    Key Record Dates
Last Update Posted: February 2, 2022
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action