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Note: This record shows only 21 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 26 November 2018
Main ID:  NCT02860286
Date of registration: 27/07/2016
Prospective Registration: Yes
Primary sponsor: Epizyme, Inc.
Public title: Study of the EZH2 Inhibitor Tazemetostat in Malignant Mesothelioma
Scientific title: A Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With Relapsed or Refractory Malignant Mesothelioma With BAP1 Loss of Function
Date of first enrolment: July 2016
Target sample size: 67
Recruitment status: Active, not recruiting
URL:  https://clinicaltrials.gov/show/NCT02860286
Study type:  Interventional
Study design:  Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
France United Kingdom United States
Contacts
Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age (at the time of consent) =18 years of age

2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

3. Has a life expectancy of >3 months

4. Has mesothelioma (pleural, peritoneal, pericardial, tunica vaginalis) of any histology
that is relapsed or refractory after treatment with at least one pemetrexed-containing
regimen

5. 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

6. Part 2: Molecular evidence of BAP1 loss of function mutation present on local
pathology, e.g., lack of nuclear BAP1 staining by immunohistochemistry (IHC) or
evidence of loss of function by gene sequencing

7. Has sufficient archival tumor tissue (a minimum of 10 slides or tumor block) available
for central retrospective testing of BAP1 status

8. Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related
clinically significant toxicities resolve to = Grade 1 per CTCAE, version 4.03 or are
clinically stable and not clinically significant, at time of enrollment

9. Prior therapy(ies), if applicable, must be completed according to the criteria below
prior to first dose of tazemetostat:

- Cytotoxic chemotherapy; at least 21 days since last dose

- Non-cytotoxic chemotherapy (e.g., small molecule inhibitor); at least 14 days
since last dose

- Monoclonal antibody; at least three half-lives since the last dose

- Non-antibody immunotherapy (e.g., tumor vaccine); at least 42 days since last
dose

- Radiotherapy, at least 14 days from last local site radiotherapy

- Hematopoietic growth factor; at least 14 days from last dose

- Investigational drug; 30 days or five half-lives, whichever is longer, from last
dose

10. Has measurable disease based on either modified RECIST [Nowak 2005] for thoracic
disease or RECIST 1.1 elsewhere

11. Has adequate hematologic (bone marrow and coagulation factors), renal, and hepatic
function as defined by criteria below:

- Hemoglobin =9 mg/dL

- Platelets =100,000/mm3 (=100 × 109/L) without platelet transfusion for 7 days

- ANC =1000/mm3 (=1.0 × 109/L) without growth factor support for 14 days

- Coagulation: Prothrombin time (PT) <1.5 × ULN and partial thromboplastin time
(PTT) <1.5 × ULN

- Creatinine < 2.0 × ULN

- Hepatic function: Conjugated bilirubin <1.5 × ULN and ALT and AST <3 × ULN

12. Has a QT interval corrected by Fridericia's formula (QTcF) =480 msec

13. Willing to provide tissue for translational research

14. Female subjects of childbearing potential must have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study drug; if the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will
be required and subject also should agree to use an adequate method of contraception
starting with screening through 30 days after the last dose of study therapy (if
sexually active).

15. Male subjects should agree to use condoms starting with the first dose of study
therapy through 30 days after the last dose of study therapy if sexually active with a
female of childbearing potential

Exclusion Criteria:

1. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste
homologue-2 (EZH2)

2. Has a history of known central nervous system metastasis

3. 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.

4. Has had major surgery within 3 weeks prior to enrollment (a percutaneous biopsy,
pleural catheter insertion, placement of central venous catheter or other minor
procedure are permitted)

5. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
and all foods that contain those fruits from time of enrollment throughout their time
on study

6. 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

7. Is currently taking any prohibited medication(s)

8. Has an active infection requiring systemic treatment

9. Has a congenital or acquired immunodeficiency, including subjects with known history
of infection with human immunodeficiency virus (HIV) NOTE: HIV-positive subjects who
are taking antiretroviral therapy are ineligible due to potential PK interactions with
tazemetostat.

10. Has known history of chronic infection with hepatitis B virus (hepatitis B surface
antigen positive) or hepatitis C virus (detectable anti-hepatitis C circulating viral
RNA)

11. Has had a deep venous thrombosis (DVT) or pulmonary embolism within the 3 months prior
to study enrollment.

NOTE: Subjects with a history of a DVT or pulmonary embolism >3 months prior to study
enrollment who are on anticoagulation therapy with low molecular weight heparin are
eligible for this study.

12. Is pregnant or breastfeeding.



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
BAP1 Loss of Function
Mesothelioma
Intervention(s)
Drug: Tazemetostat
Primary Outcome(s)
Part 1: Incidence of treatment-emergent adverse events as a measure of safety and tolerability [Time Frame: Adverse events assessed from first dose through 30 days post last dose]
Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-8) [Time Frame: Days 1 and 15]
Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-t) [Time Frame: Days 1 and 15]
Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Cmax [Time Frame: Days 1 and 15]
Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): t1/2 [Time Frame: Days 1 and 15]
Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Tmax [Time Frame: Days 1 and 15]
Part 2: To assess disease control rate (DCR) defined as number of subjects with complete response (CR), partial response (PR) and stable disease (SD) [Time Frame: 12 weeks]
Secondary Outcome(s)
Part 1 and 2: Incidence of treatment-emergent adverse events as a measure of safety and tolerability [Time Frame: Adverse events assessed from first dose through 30 days post last dose]
Part 1 and 2: Overall response rate (ORR; complete response + partial response [CR + PR]) [Time Frame: Assessed every 6 weeks for duration of study participation which is estimated to be 12 months]
Part 1 and 2: Overall survival (OS) [Time Frame: 12 weeks and 24 weeks as the time from the date of the first dose of study treatment to the date of death due to any cause assessed for up to 24 months]
Part 1 and 2: Progression-free survival (PFS) [Time Frame: 12 weeks and 24 weeks as the time from the date of the first dose of study treatment to the date of death due to any cause]
Part 1 and 2: To evaluate the duration of response (DOR) in subjects with confirmed CR or PR [Time Frame: Every 6 weeks up to disease progression or start of new anti-cancer therapy assessed for up to 12 months]
Part 1: Disease Control Rate (DCR) [Time Frame: 12 weeks]
Part 2: Changes in H3K27me3 levels in tumor tissue as assessed by IHC [Time Frame: 6 or 12 weeks]
Part 2: Population PK parameters: AUC(0-8) [Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days]
Part 2: Population PK parameters: AUC(0-t) [Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days]
Part 2: Population PK parameters: Cmax [Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days]
Part 2: Population PK parameters: t1/2 [Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days]
Part 2: Population PK parameters: Tmax [Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days]
Secondary ID(s)
EZH-203
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Results
Results available:
Date Posted:
URL:
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