A Phase II Study of ASTX727 in Patients With PRC2 Loss Malignant Peripheral Nerve Sheath Tumor (MPNST)

Memorial Sloan Kettering Cancer Center14 个研究点分布在 1 个国家目标入组 25 人2021年4月29日

适应症Malignant Peripheral Nerve Sheath Tumors (MPNST)

干预措施ASTX727

概览

阶段: 2 期
干预措施: ASTX727
疾病 / 适应症: Malignant Peripheral Nerve Sheath Tumors (MPNST)
发起方: Memorial Sloan Kettering Cancer Center
入组人数: 25
试验地点: 14
主要终点: the best clinical benefit rate (CBR)
状态: 招募中
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

The purpose of this study is to see whether the study drug ASTX727 is an effective treatment for people who have MPNST with a PCR2 mutation.

ASTX727 is a combination of two drugs (cedazuridine and decitabine) that have been designed to target cancer cells with a PCR2 mutation and to disrupt the cells' ability to survive and grow. The study researchers think that the study drug allows decitabine to work better than decitabine given alone.

注册库

clinicaltrials.gov

开始日期

2021年4月29日

结束日期

2027年4月1日

最后更新

2个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Memorial Sloan Kettering Cancer Center

责任方

Sponsor

入排标准

入选标准

•Patients must have pathologically confirmed PRC2 loss MPNSTs (e.g. IHC of loss H3K27me2 and/or H3K27me3 immunostaining, and/or inactivating mutations in EED, SUZ12, EZH2 by CLIA approved genetic assays), which are advanced, unresectable or metastatic and have progressed on at least one line of standard of care systemic therapy, or administration of cytotoxic chemotherapy is not considered in the best interest for the patient.
•Patients must be at least 16 years of age
•Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of ≤
•Disease must be measurable by RECIST 1.
•Patients must be able to take oral medications.
•Patient or legally authorized representative can understand and comply with the protocol and must sign an informed consent document.
•Adequate renal, hepatic and hematologic function as the following: serum creatinine ≤ 1.5 x upper limit of normal (ULN), total serum bilirubin ≤ 1.5 x ULN, serum AST (SGOT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor (liver metastases)), serum ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor (liver metastases)), ANC ≥ 1500/µL, platelets ≥ 75,000/µL, and hemoglobin ≥ 9 g/dL(can be transfused to achieve this). Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time \> 1.5 x ULN. Patients on a stable maintenance regimen of anticoagulation therapy for at least 30 days prior to screening may have PT/INR measurements \> 1.5 x ULN
•Patients of childbearing potential must have a negative serum pregnancy test at screening and at cycle 1 day 1 (-3 days) prior to the first dose of study therapy being administered. Female patients of childbearing potential must agree to use two reliable methods of contraception starting at signing the ICF, during and for 6 months following the last dose of study drug
•Women must agree not to breastfeed during treatment with study drug and for 2 weeks after the last dose.
•Sexually active males must agree to use a condom during intercourse and agree to not donate sperm while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid.

排除标准

•Patients have a severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
•Patients have known active brain metastasis or leptomeningeal disease.
•Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immunodeficiency virus (HIV). Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection (including undetectable viral loads while on antiviral therapy) and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
•Known active tuberculosis.
•Concurrent active inoperable locally advanced or metastatic malignancy (except for malignancies which the treating investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced MPNST).
•Patients have clinically significant cardiovascular disease, including any of the following: 1) History of acute coronary syndrome including myocardial infarction, unstable angina, CABG, coronary angioplasty or stenting \< 6 months prior to screening; 2) symptomatic chronic heart failure (New York Heart Association Criteria, Class II-IV); 3) evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities \< 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT).
•A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women) (average of triplicates).
•Left ventricular ejection fraction (LVEF) \<50% as determined by a multigated acquisition (MUGA) scan or echocardiogram.
•History of thromboembolic or cerebrovascular events ≤ 3 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
•Impairment of gastrointestinal function or gastrointestinal disease (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, ulcerative diseases, bowel resection with decreased intestinal absorption).

研究组 & 干预措施

ASTX727 (cedazuridine and decitabine)

Patients who meet the eligibility criteria will be treated with oral ASTX727 (INQOVI) on days 1-5 of each 21-day cycle with Pegfilgrastim support on day 7. A delay in the start of subsequent cycles due to holidays, weather, or other circumstances will be permitted up to 7 days and not considered a protocol deviation. Drug dosing will be interrupted for any Grade 4 adverse events or clinically significant laboratory abnormalities. For Grade 3 or 4 AE, if the AE returns to Grade 1 or baseline, the patient may be re-escalated.

干预措施: ASTX727