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

EPIZYME, INC.0 个研究点目标入组 291 人开始时间: 2021年1月27日最近更新: 2021年4月5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: 291

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): major= 18 years of age
•2.Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
•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, 4 &5)
•That is relapsed or refractory, defined as metastatic or nonresectable, locally advanced disease that has previously been treated with and progressed following approved therapy(ies), if therapy(ies) exists (Cohort 2)
•That has progressed within 6 months prior to study enrollment (Cohort 5 Expansion and Cohort 6 and 8 ONLY)
•6.Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) or other Sponsor approved 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 3,4, 5, 7& 8 (subjects with INI1-negative tumor or any solid tumor with EZH2 GOF mutation only): The following test results must be available by local laboratory:
•Morphology and immunophenotypic panel consistent with INI1-negative tumors (not applicable for solid tumors with EZH2 GOF mutation), 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, or
•Molecular evidence of EZH2 GOF mutation
•10.For Cohort 6 (subjects with epithelioid sarcoma undergoing optional tumor biopsy):
•Morphology and immunophenotypic panel consistent with epithelioid sarcoma (e.g., CD34, EMA, Keratin, and INI1)
•If providing optional biopsy: Willingness to provide informed consent to undergo pre- and post-dose biopsy
•11. 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
•12.Prior anti-cancer therapy(ies) according to the criteria described in the protocol.
•13.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).
•14.Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors as defined in the protocol.
•Please, see Protocol Synopsis for other criteria and added changes
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 266
•F.1.3 Elderly (>=65 years) yes

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 known active CNS or any leptomeningeal metastasis of primary extra-cranial tumor. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging 4 weeks prior to the first dose of study drug and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and are on stable or tapering doses of steroids for at least 7 days prior to first dose of study drug.
•NOTE: Subjects with asymptomatic brain metastases found on screening MRI may be entered into the study without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating Investigator and in the opinion of a radiation therapy or neurosurgical consultant.
•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 is 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.Has thrombocytopenia, neutropenia, or anemia of Grade =3 (per CTCAE 4.03 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and MPN (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
•NOTE: Bone marrow aspirate/biopsy will be conducted following abnormal peripheral blood smear morphology assessment conducted by central laboratory. Cytogenetic testing and DNA sequencing will be conducted following an abnormal result of bone marrow aspirate/biopsy.
•7.Has a prior history of T-LBL/T-ALL.
•8.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.
•9.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
•10.Is currently taking any prohibited medication(s) as described in the protocol.
•NOTE:Subjects with a history of hepatitis B or C with normal ALT and undetectable HBV DNA or HCV RNA are eligible for this study;
•11.Has an active infection requiring systemic treatment
•12.Is immunocompromised (ie has a congential immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV)
•13.Has known active infection with hepatitis B virus or hepatitis C virus
•Note - Subjects with a history of hepatitis B or C with normal ALT and undetectable HBV DNA or HCV RNA are eligible for this study
•14.Has had a symptomatic venous thrombosis within the 2 weeks prior to study enrollment.
•Please, see Protocol Synopsis for other criteria and added changes.

研究者

发起方

EPIZYME, INC.

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