A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma

Washington University School of Medicine1 个研究点分布在 1 个国家目标入组 21 人开始时间: 2013年10月10日最近更新: 2018年7月20日

适应症

干预措施

试验速览

阶段: 早期 1 期
状态: 已完成
发起方: Washington University School of Medicine
入组人数: 21
试验地点: 1
主要终点: Pharmacological effect of disulfiram in GBM patients

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This clinical trial studies disulfiram in treating patients with glioblastoma multiforme (GBM) who have completed radiation therapy with temozolomide. Disulfiram may block some of the enzymes needed for tumor cell growth and improve clinical outcome in GBM patients.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Diagnosis of histologically confirmed GBM (WHO grade IV).
•At least 18 years of age.
•ECOG performance status of at least
•Has received or is in the process of completing a course of definitive radiotherapy of at least 45 Gy with concurrent temozolomide (patient may be registered before completing radiotherapy as long as it is anticipated that s/he will complete at least 45 Gy).
•Eligible for and planning to receive maintenance temozolomide after completion of definitive radiotherapy plus temozolomide.
•Willing to remain abstinent from consuming alcohol while on disulfiram.
•Meets the following laboratory criteria:
•Absolute neutrophil count ≥ 1,500/mcL
•Platelets ≥ 100,000/mcL
•Hemoglobin > 9.0 g/dL (transfusion and/or ESA allowed)
•Total bilirubin ≤ 2x institutional upper limit of normal (ULN)
•AST and ALT < 3 x ULN
•Calculated creatinine clearance must be > 60 mL/min (by Cockcroft-Gault)
•Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
•Able to take oral medication.
•Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).

排除标准

•Receipt of any other investigational agents within 14 days prior to study enrollment.
•Enrolled on another clinical trial testing a novel therapy or drug.
•History of allergic reaction to disulfiram.
•Treatment with clinically significant cytochromes P450 enzyme inducers, such as phenytoin, phenobarbital, chlordiazepoxide, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram.
•Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, have New York Heart Association (NYHA) Class III or IV heart failure (Appendix B), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
•History of idiopathic seizure disorder, psychosis or schizophrenia.
•Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.

研究组 & 干预措施

Maintenance Temozolomide + Disulfram

Experimental

Beginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months. Disulfiram (dose level 0 = 500 mg PO QD or dose level 1 1000 mg PO QD) on days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity.