| Eligibility |
Inclusion Criteria:
1. Males or females are >18 years of age with body weight =40kg at the time of providing
voluntary written informed consent.
2. Voluntarily sign the written informed consent and demonstrated willingness and ability
to comply with all aspects of the protocol which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF), and
undergoing treatment and scheduled visits and examinations including follow up during
the study period,
3. Histologically and/or cytologically confirmed locally advanced (T3-T4bN0-N3M0)
non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma
4. For subjects who have experienced any clinically significant toxicity related to a
prior anticancer treatment (i.e., chemotherapy, immunotherapy, and/or radiotherapy):
at the time the subject provides voluntary written informed consent, all toxicities
have either resolved to grade 1 per NCI CTCAE Version 5.0 OR are clinically stable and
no longer clinically significant.
5. Have measurable disease as defined by RECIST 1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7. Must have a life expectancy of at least 12 weeks before enrollment.
8. Time between prior anticancer therapy and first dose of tazemetostat as follows:
Cytotoxic chemotherapy - At least 21 days Noncytotoxic chemotherapy (e.g., small
molecule inhibitor) - At least 14 days. Nitrosoureas - At least 6 weeks. Monoclonal
antibody - At least 28 days.
9. Adequate haematological functions at baseline before commencement of study medication
as defined below:
i. Absolute neutrophil count (ANC) = 1.5 x 10^9/liter without growth factor support
(filgrastim or pegfilgrastim) for at least 14 days; and ii. Platelets = 100 ×
10^9/liter evaluated at least 7 days after platelet transfusion; and iii. Hemoglobin =
9.0 x 10 /litre with blood transfusion allowed before study entry; and after treatment
commencement
10. Adequate liver function as defined at baseline before commencement of study medication
below:
Total bilirubin = 1.5 × the upper limit of normal (ULN) (except for unconjugated
hyperbilirubinemia of Gilbert's syndrome) Alkaline phosphatase (ALP) (in the absence
of bone disease), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
= 3 × ULN.
11. Adequate renal function as defined below:
Creatinine < 2.0 or calculated creatinine clearance = 35 mL/minute per the Cockcroft
and Gault formula
12. For women of childbearing potential, a negative serum or urine pregnancy test within
14 days prior to the start of treatment. Women will be considered postmenopausal if
they are amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
i.) Women < 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
and if they have luteinizing hormone and follicle-stimulating hormone levels in the
post-menopausal range for the institution or underwent surgical sterilization
(bilateral oophorectomy or hysterectomy). ii.) Women = 50 years of age would be
considered post-menopausal if they have been amenorrheic for 12 months or more
following cessation of all exogenous hormonal treatments, had radiation-induced
menopause with last menses >1 year ago, had chemotherapy-induced menopause with last
menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy,
bilateral salpingectomy or hysterectomy).
13. For female patients of childbearing potential and male patients with partners of
childbearing potential, agreement (by patient and partner) to use a highly effective
form(s) of contraception that results in a low failure rate (<1% per year) when used
consistently and correctly, starting during the screening period, continuing
throughout the entire program period, and six months for female and at least three
months for male patients after taking the last dose of tazemetostat.
Exclusion Criteria:
1. Pre-existing or co-existing epithelioid sarcoma.
2. Has a prior history of T-Cell lymphoblastic lymphoma, T-cell acute lymphoblastic
leukemia, myelodysplastic syndrome, acute myeloid leukemia, or myeloproliferative
neoplasm.
3. Have undergone a solid organ transplant.
4. Prior malignancy in the past 5 years.
5. Confirm pregnant or breastfeeding.
6. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
7. On investigational therapy within 21 days at time of recruitment.
8. Uncontrolled central nervous system (CNS) metastases requiring steroids.
9. On medications that are known potent CYP3A4 inducers/inhibitors (including St. John's
wort)
10. Unwilling to exclude Seville oranges, grapefruit juice, and grapefruit from their
diet.
11. Had major surgery within 4 weeks before the first dose of study drug. Note: Minor
surgery (e.g., minor biopsy of extracranial site, central venous catheter placement,
shunt revision) is permitted within 1 week prior to enrollment.
12. Unable to take oral medication OR have malabsorption syndrome or any other
uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, vomiting) that might
impair the bioavailability of tazemetostat.
13. Significant cardiovascular impairment: history of congestive heart failure greater
than New York Heart Association (NYHA) Class II (Appendix 3), uncontrolled arterial
hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the
first dose of study drug; or cardiac ventricular arrhythmia.
14. Have an active infection requiring systemic therapy.
15. Known hypersensitivity to any component of tazemetostat.
16. 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.
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