A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma LuDO-N

Prior treatment

• 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

Other

• Not fit enough to undergo proposed study treatment, as assessed by national PI, considering precautions defined in the latest version of the Lutathera SmPC.
• Pregnant or lactating patient
• Hydronephrosis in either kidney on baseline MRI or CT; patients can still be eligible for inclusion if urinary tract obstruction can be ruled out by renography.

• Pathology: 1.1. Histologically confirmed diagnosis of neuroblastoma, 1.2 Immunohistochemical staining for somatostatin receptors (SSTR) performed from primary tumor tissue when available
• 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
• 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: 5.1. Karnofsky > 50% (for patients > 12 years of age), 5.2. Lansky > 50% (for patients ≤ 12 years of age)
• Prior treatment 6.1. Two-week washout from any prior treatment 6.2. Patients must have recovery of hematological toxicity following previous therapy 6.3. Adequate recovery from major surgery prior to receiving study treatment
• Diagnostic imaging 7.1. 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 7.2. 123I-mIBG scintigraphy to be performed within two months prior to registration 7.3. 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 8.1. Hematology: 8.1.1. Hemoglobin, If Hb is <120 g/L then patient will receive a blood transfusion prior to commencing trial treatment 8.1.2. Absolute neutrophil count > 1.0 x 109/L 8.1.3. Absolute Platelets > 50 x 109/L 8.2. Biochemistry: 8.2.1. Bilirubin within 1.5 x ULN 8.2.2. ALT within 2.5 x ULN 8.2.3. AST within 2.5 x ULN 8.2.4. GGT within 5 x ULN 8.2.5. ALP within 5 x ULN 8.2.6. Glomerular filtration rate >50mL/min/1.73m2 assessed by a recognised method, such as inulin, 51Cr-EDTA, 99mTc-DTPA or iohexol clearance prior to registration 8.2.7. Urinary catecholamine metabolites measured within 2 months prior to registration
• Peripheral blood stem cells (PBSC) 9.1. A minimum of 2 x106 CD34+ cells/kg (optimally 6 x106 CD34+ cells/kg) must be available for each study subject prior to registration