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.
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
Drug | Synonyms | Arms |
---|
Tazemetostat | EPZ-6438 | Tazemetostat + Doxorubicin Arm |
Placebo | | Placebo + Doxorubicin Arm |
Doxorubicin HCl | | Placebo + 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
Name | Type | Description | Interventions |
---|
Tazemetostat + Doxorubicin Arm | Experimental | 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. | - Tazemetostat
- Doxorubicin HCl
|
Placebo + Doxorubicin Arm | Experimental | 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. | |
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. 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.
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
June 8, 2021