An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B Cell Lymphomas

Epizyme, Inc.0 个研究点目标入组 420 人开始时间: 2013年11月19日最近更新: 2020年7月27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: 420

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

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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

•All Subjects:
•1. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance
•status of 0 to 1. Phase 2: ECOG performance status of 0 to 2.
•2. Life expectancy = 3 months before starting tazemetostat.
•3. Subjects with a history of Hepatitis B or C are eligible on the condition
•that subjects have adequate liver function as defined by Inclusion
•Criterion #6 and are hepatitis B surface antigen negative and/or have
•undetectable hepatitis C virus (HCV RNA).
•4. Adequate renal function defined as calculated creatinine clearance =
•40 mL/min per the Cockcroft and Gault formula or local institutional
•standard formula.
•5. Adequate bone marrow function:
•a. Absolute neutrophil count (ANC)= 750/mm3 (= 0.75 × 109/L)
•b. Platelets = 75,000/mm3 (= 75 × 10*9/L)
•c. Hemoglobin = 9.0 g/dL
•6. Adequate liver function:
•a. Total bilirubin = 1.5 × the upper limit of normal (ULN) except for
•unconjugated hyperbilirubinemia of Gilbert's syndrome
•b. Alkaline phosphatase (ALP) (in the absence of bone disease), alanine
•aminotransferase (ALT), and aspartate aminotransferase (AST) = 3 ×
•ULN (= 5 × ULN if subject has liver metastases)
•7. Time between prior anticancer therapy and first dose of tazemetostat
•as indicated in the protocol.
•8. Males or females aged =18 years at the time of informed consent
•(Phase 2). Males and females aged =16 years of age at time of informed
•consent (Phase 1).
•9. Females must not be lactating or pregnant at screening or baseline
•(as documented by a negative beta-human chorionic gonadotropin [ßhCG]
•test with a minimum sensitivity of 25 IU/L or equivalent units of ßhCG).
•A separate baseline assessment is required if a negative screening
•pregnancy test was obtained more than 72 hours before the first dose of
•study drug. All females will be considered to be of childbearing potential
•unless they are postmenopausal (at least 12 months consecutively
•amenorrheic, in the appropriate age group, and without other known or
•suspected cause) or have been sterilized surgically (ie, bilateral tubal
•ligation, total hysterectomy, or bilateral oophorectomy, all with surgery
•at least 1 month before dosing). Females of childbearing potential must
•not have had unprotected sexual intercourse within 30 days prior to
•study entry and must agree to use a highly effective method of
•contraception(as per protocol), from the last menstrual period prior to
•randomization, during Treatment Cycles, and for 30 days after the final
•dose of study drug, and have a male partner who uses a condom.
•10. Male subjects must have had either a successful vasectomy OR they
•and their female partner must meet the criteria above (ie, not of
•childbearing potential OR practicing highly effective contraception and
•use a condom throughout the study period and for 30 days after study
•drug discontinuation).
•11. Voluntary agreement to provide written informed consent and the
•willingness and ability to comply with all aspects of the protocol.
•Phase 1 only (IGR and IB sites in France only):
另有 7 项未显示

排除标准

•All Subjects:
•1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
•2. Subjects with known leptomeningeal metastases or brain metastases
•or history of previously treated brain metastases.
•3. Has thrombocytopenia, neutropenia, or anemia of Grade =3 (per
•CTCAE 4.03 criteria) and any prior history of myeloid malignancies,
•including myelodysplastic syndrome (MDS).
•4. Has a prior history of T-LBL/T-ALL.
•5. Subjects taking medications that are known potent CYP3A4
•inducers/inhibitors (including St John's Wort)
•6. Subjects unwilling to exclude Seville oranges, grapefruit juice, and
•grapefruit from their diet.
•7. Any prior treatment-related (ie, chemotherapy, immunotherapy,
•radiotherapy), clinically significant toxicities have not resolved to =
•Grade 1 per CTCAE version 4.03, or prior treatment-related toxicities are
•clinically unstable and clinically significant at time of enrollment.
•8. Major surgery within 4 weeks before the first dose of study drug.
•9. Inability to take oral medication, or malabsorption syndrome or any
•other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or
•vomiting) that might impair the bioavailability of tazemetostat.
•10. Significant cardiovascular impairment: history of congestive heart
•failure greater than New York Heart Association (NYHA) Class II,
•uncontrolled arterial hypertension, unstable angina, myocardial
•infarction, or stroke within 6 months of the first dose of study drug; or
•cardiac ventricular arrhythmia.
•11. Prolongation of corrected QT interval using Fridericia's formula (QTcF)
•to > 480 msec.
•12. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
•13. Active infection requiring systemic therapy.
•14. Known hypersensitivity to any component of tazemetostat,
•prednisolone/prednisone (cohort 6 only), or inability to be
•treated with a Pneumocystis prophylaxis medication (cohort 6 only).
•15. Immunocompromised subjects, including subjects known to be
•infected with human immunodeficiency virus (HIV).
•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.
•17. Females who are pregnant or breastfeeding.
•18. Subjects who have undergone a solid organ transplant.
•Phase 2 only:
•19. Subjects with noncutaneous malignancies other than B cell
•? Exception: Subjects with another malignancy who have been diseasefree
•for 5 years, or subjects with a history of a completely resected nonmelanoma
•skin cancer or successfully treated in situ carcinoma are eligible.

研究者

发起方

Epizyme, Inc.

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