NCT02254954终止1 期
A Single-center, Open-label, Phase 1 Study of Macitentan, Radiotherapy and Temozolomide Concurrent Therapy Followed by Maintenance Therapy With Macitentan and Temozolomide in Subjects With Newly Diagnosed Glioblastoma
Actelion1 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2015年1月8日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of subjects with dose-limiting toxicities observed during the first 10 weeks of study treatment (i.e., 6 weeks of concurrent therapy with macitentan, RT and TMZ and 4 weeks of monotherapy with macitentan).
研究概览
简要总结
This is a prospective, single-center, open-label, 3+3 dose escalation Phase 1 safety study. Adults with newly diagnosed GBM or gliosarcoma will receive macitentan in addition to the standard of care treatment for GBM. The study consists of a screening period, a treatment period, and a 30-day safety follow up period. The treatment period includes 6 weeks of concurrent therapy (macitentan+RT+TMZ), 4 weeks of monotherapy (macitentan) and 12 cycles of maintenance therapy (macitentan+TMZ). The study will end when the last treated subject has completed study treatment and the 30-day safety follow-up period.
The planned duration of the study is approximately 34-38 months depending on the number of dose levels and cohorts of subjects enrolled. Subject participation in the study will be for approximately 16 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Subjects at least 18 years of age
- •Histologically proven supratentorial GBM or gliosarcoma
- •Use of effective contraception by women of childbearing potental.
- •Use of effective contraception by fertile males with a female partner of childbearing potential.
- •Interval of at least 3 weeks after biopsy or open surgery and able to begin study treatment.
- •Result from a post-operative contrast-enhanced brain MRI within 72 hours after surgery or biopsy.
- •Adequate bone marrow function
- •Karnofsky Performance Score of at least 70.
排除标准
- •Prior treatment for glioblastoma or gliosarcoma.
- •Evidence of leptomeningeal spread of glibolastoma or gliosarcoma.
- •Tumor foci below the tentorium or beyond the cranial vault.
- •Evidence of recent hemorrhage on post-operative contrast enhanced brain MRI (except hemosiderin, resolving hemorrhage changes related to surgery, presence of punctuate hemorrhage in tumor).
- •Aspartate aminotransferase or alanine aminotransferase > 3 times the upper limit of normal.
- •Supine systolic blood pressure < 100 mmHg or diastolic blood pressure < 50 mmHg.
- •Medical history of orthostatic hypotension.
- •International normalized ratio > 1.5 on anticoagulant therapy, active bleeding on low molecular weight heparin, or chronic condition with a high risk of bleeding.
- •Severe renal impairment.
- •Severe hepatic impairment.
- •Severe, active co-morbidity: (e.g. cardiac disease; respiratory disease; chronic hepatitis; hemtological and bone marrow diseases; severe malabsoprtion; human immunodeficiency virus).
- •No concurrent strong CYP3A4 inducers or inhibitors.
- •No investigational drug within 4 weeks of starting study treatment.
- •Any life-threatening condition that could affect protocol compliance.
研究组 & 干预措施
Macitentan in combination with RT & TMZ
Experimental
Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ.
干预措施: Macitentan in combination with RT and TMZ (Drug)
结局指标
主要结局
Number of subjects with dose-limiting toxicities observed during the first 10 weeks of study treatment (i.e., 6 weeks of concurrent therapy with macitentan, RT and TMZ and 4 weeks of monotherapy with macitentan).
时间窗: Start of treatment to week 10
次要结局
- Plasma concentrations of macitentan and its metabolite(Baseline, Weeks 2 and 6)
- Area under the plasma concentration-time curve (AUCτ) for macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher(Week 4)
- Time to reach peak plasma concentration (Tmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher(Week 4)
- Number of adverse events (per Common Terminology Criteria for Adverse Events [CTCAE] criteria, version 4.03]) leading to premature discontinuation of study treatment(Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up)
- Number of subjects with marked laboratory abnormalities or abnormal electrocardiogram (ECG) findings(Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up)
- Change from baseline in pulse rate, systolic & diastolic blood pressure(Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days follow-up)
- Exploratory efficacy endpoint of proportion of subjects with progression free survival (PFS) at 6 and 12 months(6 and 12 months after the start of treatment)
- Plasma concentrations of endothelin-1(Baseline, Weeks 2, 6, and 10)
- Peak plasma concentration (Cmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher(Week 4)
- Number of adverse events (per CTCAE] criteria, version 4.03]) as a measure of safety and tolerability.(Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up)
研究者
研究点 (1)
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