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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02601950




Registration number
NCT02601950
Ethics application status
Date submitted
21/10/2015
Date registered
11/11/2015

Titles & IDs
Public title
A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
Scientific title
A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma
Secondary ID [1] 0 0
2015-002469-41
Secondary ID [2] 0 0
EZH-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Rhabdoid Tumors (MRT) 0 0
Rhabdoid Tumors of the Kidney (RTK) 0 0
Atypical Teratoid Rhabdoid Tumors (ATRT) 0 0
Selected Tumors With Rhabdoid Features 0 0
Synovial Sarcoma 0 0
INI1-negative Tumors 0 0
Malignant Rhabdoid Tumor of Ovary 0 0
Renal Medullary Carcinoma 0 0
Epithelioid Sarcoma 0 0
Poorly Differentiated Chordoma (or Other Chordoma With Sponsor Approval) 0 0
Any Solid Tumor With an EZH2 GOF Mutation 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

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

Experimental: Open-label Tazemetostat - All cohorts will receive 800 mg oral Tazemetostat twice a day in continuous 28-day cycles.


Treatment: Drugs: Tazemetostat
Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response rate (ORR) in Cohorts 1,3,4,5,6 and 7
Timepoint [1] 0 0
Day 1 and 15 of Cycle 1 and Cycle 2, Day 1 of Cycle 3, every 28 Days thereafter assessed maximum up to 2 years
Primary outcome [2] 0 0
Progression-free survival (PFS) rate in Cohort 2
Timepoint [2] 0 0
16 weeks of treatment
Primary outcome [3] 0 0
Number of participants with adverse events (AEs) in Cohort 8
Timepoint [3] 0 0
Through study completion, an average of 2 years
Primary outcome [4] 0 0
Percentage of Participants with Clinically Significant changes in Laboratory Parameters (blood chemistry, hematology and coagulation)
Timepoint [4] 0 0
Up to 2 years.
Secondary outcome [1] 0 0
Duration of response (DOR) in all Cohorts
Timepoint [1] 0 0
Assess every 8 weeks for duration of study participation which is estimated to be 2 years.
Secondary outcome [2] 0 0
Disease control rate (DCR) in Cohort 5, 6 and 8
Timepoint [2] 0 0
32 weeks of treatment
Secondary outcome [3] 0 0
Objective Response Rate (ORR) in Cohort 2
Timepoint [3] 0 0
Day 1 and 15 of Cycle 1 and Cycle 2, Day 1 of Cycle 3, every 28 Days thereafter assessed maximum up to 2 years
Secondary outcome [4] 0 0
Overall survival (OS) in all cohorts
Timepoint [4] 0 0
24, 32 and 56 weeks of treatment
Secondary outcome [5] 0 0
Overall survival for each cohort
Timepoint [5] 0 0
Weeks 24, 32, 56, and at end of study, an average of 2 years.

Eligibility
Key inclusion criteria
1. Age (at the time of consent/assent): =18 years of age
2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
3. Has provided signed written informed consent
4. Has a life expectancy of >3 months
5. Has a malignancy:

* For which there are no standard therapies available (Cohorts 1, 3, 4 and 5)
* That is relapsed or refractory after treatment with an approved therapy(ies), defined as metastatic or non-resectable, locally advanced disease that has previously been treated with and progressed following approved therapy(ies) (Cohort 2)

* That has progressed within 6 months prior to study enrollment (Cohort 5 Expansion, Cohort 6 and Cohort 8 ONLY)
6. Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA/College of American Pathologists (CAP) or equivalent laboratory certification
7. For Cohort 1 (rhabdoid tumors only), the following test results must be available by local laboratory: morphology and immunophenotypic panel consistent with rhabdoid tumors, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss or mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
8. For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
9. For Cohort 3, 4, 5, 7 and 8 (subjects with INI1-negative/aberrant tumors or any solid tumor with EZH2 GOF mutation only), the following test results must be available by local laboratory: Morphology and immunophenotypic panel consistent with INI1-negative tumors (not applicable for solid tumors with EZH2 GOF mutation), and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss or mutation when INI1 IHC is equivocal or unavailable, or molecular evidence of EZH2 GOF mutation
10. For Cohort 6 (subjects with ES undergoing optional tumor biopsy) only:

* Morphology and immunophenotypic panel consistent with ES (e.g., CD34, EMA, Keratin, and INI1)
11. Has all prior treatment (i.e. chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to =Grade 1 per CTCAE version 4.0.3 or are clinically stable and not clinically significant, at time of enrollment.
12. Prior anti-cancer therapy(ies), if applicable, must be completed according to the criteria below:

* Chemotherapy: cytotoxic (At least 14 days since last dose of chemotherapy prior to first dose of tazemetostat)
* Chemotherapy: nitrosoureas (At least 6 weeks since last dose of nitrosoureas prior to first dose of tazemetostat)
* Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) (At least 14 days since last dose of non-cytotoxic chemotherapy prior to first dose of tazemetostat)
* Monoclonal antibody(ies) (At least 28 days since the last dose of any monoclonal antibody prior to first dose of tazemetostat)
* Immunotherapy (e.g. tumor vaccine) (At least 42 days since last dose of immunotherapy agent(s) prior to first dose of tazemetostat)
* Radiotherapy (RT) (At least 14 days from last local site RT prior to first dose of tazemetostat/At least 21 days from stereostatic radiosurgery prior to first dose of tazemetostat/At least 12 weeks from craniospinal, =50% radiation of pelvis, or total body irradiation prior to first dose of tazemetostat)
* High dose therapy with autologous hematopoietic cell infusion (At least 60 days from last infusion prior to first dose of tazemetostat)
* Hematopoietic growth factor (At least 14 days from last dose of hematopoietic growth factor prior to first dose of tazemetostat)
13. Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing
14. Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors
15. Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function.
16. For subjects with CNS Tumors only, subject must have seizures that are stable, not increasing in frequency or severity and controlled on current anti-seizure medication(s) for a minimum of 21 days prior to the planned first dose of tazemetostat
17. Has a shortening fraction of >27% or an ejection fraction of =50% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan and New York Heart Association (NYHA) Class =2
18. Has a QT interval corrected by Fridericia's formula (QTcF) =480 msec
19. Female subjects of childbearing potential must:

* Have a negative beta-human chorionic gonadotropin (ß-hCG) pregnancy test at time of screening and within 14 days prior to planned first dose of tazemetostat and
* Agree to use effective contraception from a minimum of 7 days prior to first dose until 6 months following the last dose of tazemetostat and have a male partner who uses a condom, or
* Practice true abstinence or have a male partner who is vasectomized
20. Male subjects with a female partner of childbearing potential must:

* Be vasectomized, or
* Agree to use condoms as defined in Section 8.6.2, from first dose of tazemetostat until 3 months following the last dose of tazemetostat, or
* Have a female partner who is NOT of childbearing potential
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
2. Has 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 tazemetostat
3. Has known active CNS or any leptomeningeal metastasis of primary extra-cranial tumor.
4. Has had a prior malignancy other than the malignancies under study - EXCEPTION: A subject who has been disease-free for 5 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible
5. Has had major surgery within 3 weeks prior to enrollment
6. Has Thrombocytopenia, neutropenia, or anemia of Grade =3 (per CTCAE 4.03 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and MPN (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
7. Has a prior history of T-LBL /T-ALL
8. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
9. Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
10. Is currently taking any prohibited medication(s)
11. Has an active infection requiring systemic treatment
12. Is immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV)
13. Has known active infection with hepatitis B virus or hepatitis C virus
14. Has had a symptomatic venous thrombosis within 2 weeks prior to study enrollment -
15. For subjects with CNS involvement (primary tumor or metastatic disease), have any active bleeding or new intratumoral hemorrhage of more than punctuate size of screening MRI obtained within 14 days of starting study drug or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
16. Has known hypersensitivity to any of the component of tazemetostat or other inhibitor(s)of EZH2
17. Is unable to take oral medications, or has a malabsorption syndrome or any uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that would limit compliance with study requirements.
18. Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.
19. For female subjects of childbearing potential: Is pregnant or nursing
20. For male subjects: Is unwilling to adhere to contraception criteria from time of enrollment in the study to at least 3 months after last dose of tazemetostat.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/02/2024
Sample size
Target
Accrual to date
Final
267
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Metro South Hospital and Health Service via Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
QLD 4102 - Woolloongabba
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
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
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
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux
Country [19] 0 0
France
State/province [19] 0 0
Lyon
Country [20] 0 0
France
State/province [20] 0 0
Paris Cedex 13
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Villejuif
Country [23] 0 0
Germany
State/province [23] 0 0
Augsburg
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Italy
State/province [25] 0 0
Milano
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taipei City
Country [27] 0 0
United Kingdom
State/province [27] 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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: https://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/NCT02601950