Phase I Study of Immunotoxin, MR1-1
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose and dose limiting toxicity
研究概览
简要总结
Purpose of the study:
Primary Objective: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of MR1-1KDEL when delivered intracerebrally by convection-enhanced delivery (CED) in patients with supratentorial malignant brain tumors.
Secondary Objective: Document any radiographic responses associated with intracerebral CED of MR1-1KDEL.
Hypothesis: The investigators believe that MR1-1KDEL will be an effective anti-tumor agent for patients with supratentorial malignant brain tumors when delivered by CED.
Design & procedures: This protocol is designed primarily to determine the MTD and DLT of a novel, tumor-specific immunotoxin, MR1-1KDEL. MR1-1KDEL will be delivered intracerebrally by CED using 2 intracerebral catheters with at least one catheter placed within the enhancing portion of the tumor. 124I-labeled albumin will be co-infused with gadolinium and PET and MRI images will be obtained at the conclusion of the infusion to monitor volume of drug distribution and leakage into the CSF space.
Based on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two to four catheters. A total of 144 mLs of drug solution will be delivered over 72 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg). At least 3 patients will be enrolled in each cohort. All patients in a given cohort will be observed for at least two weeks following infusion of the study drug before patients in the next cohort are treated. If no patients in a given cohort experience a DLT, the dose will be escalated in the next cohort. If 1 out of 3 patients in a given cohort experience DLT, 3 additional patients will be entered in that cohort. If 2 patients develop a DLT in any cohort of 3 or 6 patients, the previous dose will be declared the MTD. Patients will be followed at 1, 3, 6, 9, 12 month intervals for toxicity and adverse events, radiographic response, and survival. Patients will be off study when progressive disease is documented.
Risk/benefit assessment: This is an experimental study and unforeseeable or unexpected risks may be involved.
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
- •Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable disease (>0.5cm).
- •Patient will have completed some form of radiation therapy prior to toxin treatment.
- •Karnofsky Performance score >
- •The presence of the target antigen, EGFRvIII, must be identified on tumor tissue by immunohistochemistry.
- •Platelet count > 100 x 109/L; PTT and PT < 120% of normal range.
- •Creatinine < 120% of normal range.
- •Total bilirubin, SGOT, SGPT,alkaline phosphatase < 300% of normal range.
排除标准
- •Patients who are pregnant, breast-feeding, or unwilling to practice an effective method of birth control.
- •Patients with known potentially anaphylactic allergic reactions to iodine or gadolinium-DTPA.
- •Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods or plates).
- •Patients that have not recovered from the toxic effects of prior chemotherapy and/or radiation therapy.
- •Patients with an impending, life-threatening cerebral herniation syndrome.
- •Patients with subependymal or CSF disease.
- •Patients who are under the age of 18 years.
结局指标
主要结局
Maximum tolerated dose and dose limiting toxicity
时间窗: continual
次要结局
- Disease Progression(continual)
研究者
Darell D. Bigner, MD, PhD
Director, The Preston Robert Tisch Brain Tumor Center at Duke
Duke University