A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 13
- 主要终点
- Incidence of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
Adults with leptomeningeal metastasis from solid tumors will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.
详细描述
Part 1 is a dose-escalation phase with a 3+3 sequential-group design in which patients will receive a dosimetry dose followed by maximum of five 5-week cycles of treatment doses of intracerebroventricular 177Lu-DTPA-omburtamab.
Part 2 is a cohort-expansion phase in which patients will receive a treatment at the recommended dose determined in Part 1, until confirmed LM progression, unacceptable toxicity, or for maximum of 5 cycles, whichever comes first; however, the total number of cycles will be determined based upon data from Part 1 (e.g., the dosimetry data) to minimize the risk of radiation necrosis and decreased neurological function End of treatment will take place within 5 weeks after the last cycle and thereafter the patients will be enter the follow-up period. The patients will be followed for up until one year after first dose (Part 1) and 2 years after first dose (Part 2).
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
- •Primary ductal or lobular breast cancer, non-small cell lung cancer, or malignant melanoma
- •Type I or Type II LM with a "confirmed" or "probable" diagnosis according to EANO-ESMO guidelines 2017
- •Life expectancy more than 2 months, as judged by the Investigator
- •ECOG Performance status 0, 1, or 2
- •Acceptable hematological status and liver and kidney function
- •Written informed consent obtained in accordance with local regulations
- •Presence of an intracerebroventricular access device before first dosing
排除标准
- •Obstructive or symptomatic communicating hydrocephalus
- •Progressive systemic (extra-leptomeningeal) disease
- •Uncontrolled life-threatening infection
- •Ventriculo-peritoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts
- •Received craniospinal irradiation (for intraparenchymal or dural metastases) or intrathecal cytotoxic anti-cancer therapy less than 3 weeks prior to first dose of 177Lu-DTPA-omburtamab
- •Severe non-hematologic organ toxicity; specifically, any renal, cardiac, hepatic, pulmonary, or gastrointestinal system toxicity Grade 3 or above prior to enrolment
- •Grade 4 nervous system disorder. Hearing loss or stable neurological deficits due to brain tumor are allowed
- •Unacceptable coagulation function prior to first dosing defined as INR Grade 2 or above
- •Female of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant, or are not using highly effective contraceptive methods or male who is not using highly effective contraceptive method
- •Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.
- •Smallest diameter of treated or untreated nodular or linear leptomeningeal metastasis >0.5 cm on MRI (Part 2 only)
结局指标
主要结局
Incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 1 year
Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0. The maximum tolerated dose and the recommended phase 2 dose (RP2D) will be determined in Part 1
Incidence of AEs and SAEs
时间窗: 2 years
In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1
次要结局
- Elimination Half Life in serum(7 weeks)
- Maximum radioactivity count of lutetium-177 in blood(2 weeks)
- Dosimetry analysis of lutetium-177(2 weeks)
- Investigator-assessed Duration of Response (DoR)(2 years)
- Maximum Plasma Concentration [Cmax] in CSF(7 weeks)
- Response(2 years)
- Elimination half-life of lutetium-177 radioactivity in blood(2 weeks)
- Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)(2 weeks)
- Maximum Plasma Concentration [Cmax] in serum(7 weeks)
- Elimination Half Life in CSF(7 weeks)
- Overall Survival (OS)(2 years)
- Progression-free Survival (PFS)(2 years)