A Phase 2, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects with Relapsed or Refractory BAP1 deficientMalignant Mesothelioma

Epizyme, Inc.0 个研究点目标入组 67 人开始时间: 2016年6月28日最近更新: 2019年6月30日

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: 67

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

入选标准

•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:
•a. Cytotoxic chemotherapy; at least 21 days since last dose
•b. Non-cytotoxic chemotherapy (e.g., small molecule inhibitor); at least 14 days since last dose
•c. Monoclonal antibody; at least three half-lives since the last dose
•d. Non-antibody immunotherapy (e.g., tumor vaccine); at least 42 days since last dose
•e. Radiotherapy, at least 14 days from last local site radiotherapy
•f. Hematopoietic growth factor; at least 14 days from last dose
•g. 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:
•a. Hemoglobin =9 mg/dL
•b. Platelets =100,000/mm3 (=100 × 109/L) without platelet transfusion for 7 days
•c. ANC =1000/mm3 (=1.0 × 109/L) without growth factor support for 14 days
•d. Coagulation: Prothrombin time (PT) <1.5 × ULN and partial thromboplastin time (PTT) <1.5 × ULN
•e. Creatinine < 2.0 × ULN
•f. 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 starti

排除标准

•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

研究者

发起方

Epizyme, Inc.

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