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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04204941




Registration number
NCT04204941
Ethics application status
Date submitted
11/12/2019
Date registered
19/12/2019

Titles & IDs
Public title
Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma
Scientific 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
Secondary ID [1] 0 0
2019-003648-55
Secondary ID [2] 0 0
EZH-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Soft-tissue Sarcoma 0 0
Advanced Epithelioid Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tazemetostat
Treatment: Drugs - Doxorubicin HCl
Treatment: Drugs - Tazemetostat
Treatment: Drugs - Placebo
Treatment: Drugs - Doxorubicin HCl

Experimental: Phase 1b: Open-label Tazemetostat and Phase 3: Tazemetostat + Doxorubicin Arm - Phase 1b: On cycle 1 day -1, participants will receive a single morning dose of tazemetostat at the assigned dose level. Participants will receive doxorubicin 75 mg/m2 intravenously (IV) on day 1 of each cycle for up to 6 cycles.

Tazemetostat will be escalated from a starting dose of 400 mg twice daily PO to 600 mg twice daily PO to 800 mg twice daily.

Phase 3:

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.

Placebo comparator: Phase 3: 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.


Treatment: Drugs: Tazemetostat
400 mg, 600 to 800 mg of Tazemetostat will be administered twice daily.

Treatment: Drugs: Doxorubicin HCl
75mg/m2 intravenous injection day 1 of each cycle for up to 6 cycles

Treatment: Drugs: 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.

Treatment: Drugs: Placebo
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

Treatment: Drugs: Doxorubicin HCl
75mg/m2 intravenous injection day 1 of each cycle for up to 6 cycles
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
1 Cycle/21 days
Primary outcome [2] 0 0
Progression free survival (PFS)
Timepoint [2] 0 0
Through study completion, an average of two years.
Secondary outcome [1] 0 0
Phase 1b: Pharmacokinetics (PK) of tazemetostat when administered in combination with doxorubicin in participants with soft tissue sarcoma (STS): Area under the Plasma Concentration Time Curve from time 0 to 24 hours (AUC0-24)
Timepoint [1] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [2] 0 0
Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in participants with STS: Area under the Plasma Concentration Time Curve From time 0 to the last observable concentration (AUC0- last)
Timepoint [2] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [3] 0 0
Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in Pparticipants with STS: The maximum observed concentration (Cmax).
Timepoint [3] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [4] 0 0
Phase 3: Overall Survival (OS)
Timepoint [4] 0 0
Through study completion, an average of two years.
Secondary outcome [5] 0 0
Phase 3: Incidence of Adverse Events (AEs)
Timepoint [5] 0 0
Through study completion, an average of two years.
Secondary outcome [6] 0 0
Phase 3: PFS
Timepoint [6] 0 0
Through study completion, an average of two years.
Secondary outcome [7] 0 0
Disease control rate (DCR)
Timepoint [7] 0 0
Through study completion, an average of two years
Secondary outcome [8] 0 0
Objective response rate (ORR)
Timepoint [8] 0 0
Through study completion, an average of two years
Secondary outcome [9] 0 0
Duration of treatment (DOR)
Timepoint [9] 0 0
Through study completion, an average of two years
Secondary outcome [10] 0 0
Change from baseline in European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQC-30)
Timepoint [10] 0 0
Through study completion, an average of two years
Secondary outcome [11] 0 0
PFS2
Timepoint [11] 0 0
Through study completion, an average of two years
Secondary outcome [12] 0 0
Time to first subsequent anti-cancer therapy ((TFST
Timepoint [12] 0 0
Through study completion, an average of two years
Secondary outcome [13] 0 0
Population PK parameters of tazemetostat when administered in combination with doxorubicin: Oral clearance (CL/F)
Timepoint [13] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [14] 0 0
Population PK parameters of tazemetostat when administered in combination with doxorubicin: oral volume of distribution (Vss).
Timepoint [14] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [15] 0 0
Population PK parameters of tazemetostat when administered in combination with doxorubicin: Area Under the Curve at steady state (AUCss)
Timepoint [15] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [16] 0 0
Population PK parameters of tazemetostat when administered in combination with doxorubicin: trough concentration (Ctrough)
Timepoint [16] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Secondary outcome [17] 0 0
Population PK parameters of tazemetostat when administered in combination with doxorubicin: Cmax
Timepoint [17] 0 0
Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy

Eligibility
Key inclusion criteria
Inclusion Criteria

Participants 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 participants of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception
11. Participants diagnosed with human immunodeficiency virus (HIV) are eligible to participate in the study if their infection is well controlled on anti-retroviral therapy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Participants 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. Participants 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. Participants 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 participant's participation in this study OR interfere with their ability to receive study treatment or complete the study.
18. Female participants who are pregnant or breastfeeding.
19. Participants who have undergone a solid organ transplant.
20. Participants with malignancies other than STS (phase 1b) or ES (Phase 3 only).
21. Participants housed in an institution by order of the authorities or courts.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2030
Actual
Sample size
Target
164
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Taiwan
State/province [15] 0 0
Taipei
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Epizyme, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ipsen Recruitment Enquiries
Address 0 0
Country 0 0
Phone 0 0
See e mail
Fax 0 0
Email 0 0
clinical.trials@ipsen.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
When will data be available (start and end dates)?
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
Available to whom?
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://vivli.org/members/ourmembers/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04204941