A Phase II Trial of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-risk Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 10
- 主要终点
- Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) - 1 months after End of Treatment
研究概览
简要总结
The LuDO-N Trial is a multi-centre phase II clinical trial on 177Lu-DOTATATE treatment of recurrent or relapsed high-risk neuroblastoma in children. The LuDO-N Trial builds on the experience from the previous LuDO Trial and utilises an intensified dosing schedule to deliver 2 doses over a 2-week period, in order to achieve a maximal effect on the often rapidly progressing disease. This strategy requires a readiness for autologous stem cell transplantation in all patients, but is not anticipated to increase the risk of long-term sequelae, since the cumulative radiation dose remains unchanged. The primary aim of the study is to assess the response to 177Lu-DOTATATE treatment at 1 and 4 months after ende of treatment. Secondary aims are to assess survival and treatment-related toxicity. Additional aim are to correlate tumour dosimetry with response, correlate SSTR-2 expression with 68Ga-DOTATATE uptake and to correlate the uptake with the treatment response.
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 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathology 1.
- •Histologically confirmed diagnosis of neuroblastoma 1.
- •Immunohistochemical staining for somatostatin receptors (SSTR) performed from primary tumor tissue when available
- •Relapsed or primary refractory high-risk neuroblastoma: INSS stage 4 disease or INRGSS stage M disease
- •Age >18 months at the time of enrolment into this study
- •Life expectancy of greater than 3 months
- •Performance Status 5.
- •Karnofsky > 50% (for patients > 12 years of age) 5.
- •Lansky > 50% (for patients ≤ 12 years of age)
- •Prior treatment 6.
- •Two-week washout from any prior treatment 6.
- •Patients must have recovery of hematological toxicity following previous therapy 6.
- •Adequate recovery from major surgery prior to receiving study treatment
- •Diagnostic imaging 7.
- •Uptake in the primary tumor or metastatic tumour deposits on 68Ga-DOTATATE PET/CT at least higher than the liver uptake and performed within two months prior to registration 7.
- •123I-mIBG scintigraphy to be performed within two months prior to registration 7.
- •CT or MRI of the primary tumor and bulky metastatic sites within two months prior to registration
- •Laboratory requirements to be performed within 7 days prior to commencing trial treatment 8.
- •Hematology: 8.1.
- •Hemoglobin, If Hb is <120 g/L then patient will receive a blood transfusion prior to commencing trial treatment 8.1.
- •Absolute neutrophil count > 1.0 x 109/L 8.1.
- •Absolute Platelets > 50 x 109/L 8.
- •Biochemistry: 8.2.
- •Bilirubin within 1.5 x ULN 8.2.
- •ALT within 2.5 x ULN 8.2.
- •AST within 2.5 x ULN 8.2.
- •GGT within 5 x ULN 8.2.
- •ALP within 5 x ULN 8.2.
- •Glomerular filtration rate >50mL/min/1.73m2 assessed by a recognised method, such as inulin, 51Cr-EDTA, 99mTc-DTPA or iohexol clearance and performed within 2 months prior to registration 8.2.
- •Urinary catecholamine metabolites measured within 2 months prior to registration
- •Peripheral blood stem cells (PBSC) 9.
- •A minimum of 2 x106 CD34+ cells/kg (optimally 6 x106 CD34+ cells/kg) must be available for each study subject prior to registration
- •Written informed consent from patient and/or parent(s) or legal guardian(s) in accordance with national regulations, prior to registration or any trial-related screening procedures
排除标准
- •Not fit enough to undergo proposed study treatment, as assessed by national PI, considering precautions defined in the latest version of the 177Lutetium-DOTATATE SmPC.
- •Pregnant or lactating patient
- •Concurrent treatment with any anti-tumor agents
- •Prior treatment with other radiolabeled somatostatin analogues
- •Hypersensitivity to any component of the investigational drug 177Lutetium-DOTATATE
- •Treatment with long-acting somatostatin analogues within 30 days, or with short-acting somatostatin analogues within 24 hours prior the administration of 177Lutetium-DOTATATE
结局指标
主要结局
Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) - 1 months after End of Treatment
时间窗: 1 months following end of treatment
Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC)
次要结局
- Progression-free survival(Time from registration to progression or death, up to 5 years following end of treatment)
- Number and severity of treatment-related adverse events(Up to 5 years after end of treatment)
- Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) - 4 months after End of Treatment(4 months following end of treatment)
- Overall survival - up to 5 years after End of Treatment(Time from registration to the the date of death, up to 5 years following end of treatment)
研究者
Jakob Stenman
Consultant Pediatric Surgeon, Associate Professor
Karolinska University Hospital