A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF in a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD).
研究概览
简要总结
This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis.
详细描述
Neoplastic meningitis refers to the deposition of malignant cells in the lining (leptomeninges) of the brain and spine. Neoplastic meningitis from solid tumors most often occurs in patients with advanced systemic disease who have failed prior chemotherapy; it is also frequent in patients with CNS parenchymal metastasis. Patient survival remains low, and better treatments are needed to penetrate the blood brain barrier and treat the entire neuraxis.
RTA 744 is a close chemical analogue of the well characterized anti-cancer agent doxorubicin. Unlike doxorubicin, RTA 744 has shown ability to cross the blood brain barrier and to achieve high concentration in CNS tumor tissue in animal models. Dose escalation will continue as pre-determined until first occurrence of a dose-limiting toxicity. Maximum tolerated dose will be determined as defined in protocol.
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
- •Histologic confirmation of primary malignancy. All primary tumor types may be enrolled.
- •Neoplastic meningitis/leptomeningeal metastasis refractory to conventional therapy with presence of tumor cells on cytology, OR neuroimaging evidence of leptomeningeal tumor by MRI.
- •Not eligible for higher priority clinical trial.
- •Have recovered from side effects of any surgical resection.
- •A stable dose of steroid for at least 7 days prior to the Gd-MRI.
- •Karnofsky Performance Status (KPS) of ≥
- •Laboratory Parameters: ANC ≥ 1.5 x 109/L; Hgb ≥ 9 g/dl; Platelets ≥ 100 x 109/L; AST and ALT ≤ 3.0 x ULN; Serum bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN; 24 hour creatinine clearance ≥ 50 ml/min
- •Life expectancy of at least 8 weeks.
- •Written informed consent obtained.
排除标准
- •Concurrent therapy for leptomeningeal disease or other malignancy.
- •Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
- •Cumulative doses: doxorubicin > 450 - 550 mg/m2, epirubicin > 800-1000 mg/m2, idarubicin >130-150 mg/m2 and daunorubicin > 400-550 mg/m
- •Anticonvulsant medications or other types of medications which are known to induce the CYP450 enzymes.
- •Pregnancy or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control
- •Total 24 hour urinary protein > 500 mg.
- •Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
- •Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type
- •Myocardial infarction ≤ 6 months prior
- •History of CHF or arrhythmias
- •Therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed)
- •Investigational drugs less than 4 weeks prior; intrathecal chemotherapy within 2 weeks prior; systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine); radiation therapy within 2 weeks prior; any medication known to cause QT interval prolongation
- •Any surgery <2 weeks prior
研究组 & 干预措施
RTA 744
RTA 744 injection administered intravenously for a maximum of 18 cycles (54 weeks). Dose escalation based on four dose levels and occurance of dose limiting toxicity (DLT).
干预措施: RTA 744 (Drug)
结局指标
主要结局
Characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF in a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD).
时间窗: end of study
Determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.
时间窗: evaluation at end of cycle 1 for each cohort
次要结局
- Document any potential antitumor activity.(after every even numbered treatment cycle)
- Correlate pharmacokinetic information with clinical (efficacy and safety) responses.(end of study)