A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects with INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma

Epizyme, Inc.0 个研究点目标入组 90 人开始时间: 2016年1月15日最近更新: 2024年1月8日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Epizyme, Inc.
入组人数: 90

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1.Age (at the time of consent/assent): =16 years of age
•2.Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix 1)
•NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status.
•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)
•That is relapsed or refractory after treatment with an approved therapy(ies) (Cohort 2)
•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 (subjects with 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 test results must be available by local laboratory:
•Morphology consistent with synovial sarcoma, 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 (subjects with INI1-negative/aberrant tumor only): The following test results must be available by local laboratory:
•Morphology and immunophenotypic panel consistent with INI1-negative tumors, 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
•10.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, at time of enrollment
•11.Has completed a prior therapy(ies) according to the criteria described in the protocol.
•12.Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing of IHC and/or cytogenetics/FISH and/or DNA mutation analysis (required for study entry but enrollment based on local results).
•13.Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors as defined in the protocol.
•14.Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function as defined by criteria in the protocol.
•15.For subjects with ATRT 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
•16.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 less than or equal to 2
•17.Has a QT interval corrected by Fridericia's formula (QTcF) =480 msec
•18.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, as defined in the protocol, from start of screening until 30 days followi

排除标准

•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 CNS or leptomeningeal metastasis of primary extra-cranial tumor.
•NOTE: Only subjects with ATRT as the primary tumor are permitted.
•4.Has had a prior malignancy other than the malignancies under study
•Exception: 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 are eligible.
•5.Has had major surgery within 3 weeks prior to enrollment
•NOTE: Minor surgery (e.g., minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment.
•6.Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study.
•7.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
•8.Is currently taking any prohibited medication(s) as described in the protocol.
•9.Has an active infection requiring systemic treatment
•10.Is immunocompromised (ie has a congential immunodeficiency), including subjects 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.
•11.Has known history of chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable HCV RNA)
•12.Has had a symptomatic venous thrombosis within the 3 months prior to study enrollment.
•NOTE: Subjects with a history of a deep vein thrombosis >3 months prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study.
•13.For subjects with ATRT only: Have =3 foci of punctate hemorrhage, any active bleeding, or intratumoral hemorrhage at time of enrollment or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents.
•14.Has known hypersensitivity to any of the components of tazemetostat or other inhibitor(s) of EZH2
•15.Is unable to take oral medications, malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that might impair the bioavailability of tazemetostat
•16.Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.
•17.For female subjects of childbearing potential: Is pregnant or nursing
•18.For male subjects: Is unwilling to adhere to contraception criteria from time of enrollment in study to at least 30 days after last dose of tazemetostat.

研究者

发起方

Epizyme, Inc.

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