A Phase I/II Dose-escalation and Expansion Cohort Trial of Intracerebroventricular Radioimmunotherapy Using 177Lu-DTPA-Omburtamab in Pediatric and Adolescent Patients With Recurrent or Refractory Medulloblastoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 10
- 主要终点
- Dose Limiting Toxicities (DLTs) Part 1
研究概览
简要总结
Children and adolescents diagnosed with medullablastoma and with recurrent or refractory to frontline therapy 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 two 5-week cycles of treatment doses of intracerebroventricular 177Lu-DTPA-omburtamab.
Part 2 is a cohort-expansion phase in which patients will receive a maximum of five 5-week cycles of intracerebroventricular 177Lu-DTPA-omburtamab at the recommended dose determined in Part 1.
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 to 2 years after last dose.
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
- 3 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of medulloblastoma.
- •SHH, Group 3, or Group 4 according to World Health Organisation (WHO) 2016 classification.
- •Recurrent (maximum of 2 recurrences for Part 1 and 1 recurrence for Part 2) or refractory to frontline therapy. Prior frontline or second line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens.
- •Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously.
- •Performance status score of 50 to 100 on Lansky (less than 16 years) or Karnofsky (16 years or older) scales.
- •Life expectancy of at least 3 months, as judged by the Investigator.
- •Acceptable hematological status and liver and kidney function.
排除标准
- •Obstructive or symptomatic communicating hydrocephalus as determined by Ommaya patency/cerebrospinal fluid (CSF) flow study.
- •Residual disease (nodular or linear) measuring > 15 mm in the smallest diameter.
- •Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts.
- •Grade 4 nervous system disorder. Stable neurological deficits (due to brain tumor or surgery) or hearing loss are allowed.
- •Uncontrolled life-threatening infection.
- •Received radiation therapy less than 3 weeks prior to the screening visit.
- •Received systemic or intrathecal cytotoxic chemotherapy or intrathecal immunotherapy (corticosteroids not included) less than 3 weeks prior to the screening visit.
- •Received any prior anti-B7-H3 treatment.
- •Non-hematologic organ toxicity Grade 3 or above; specifically, any renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity.
- •Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.
研究组 & 干预措施
177Lu-DTPA-omburtamab
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).
干预措施: 177Lu-DTPA-omburtamab (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLTs) Part 1
时间窗: Days 1 through 35 in cycle 1
Summary of DLTs in DLT evaluable subjects.
次要结局
未报告次要终点