177Lutetium-DOTATATE in Children with Primary Refractory or Relapsed High-risk Neuroblastoma

Inclusion Criteria:

1. Pathology 1.1. Histologically confirmed diagnosis of neuroblastoma 1.2.Immunohistochemical staining for somatostatin receptors (SSTR) performed fromprimary tumor tissue when available

2. Relapsed or primary refractory high-risk neuroblastoma: INSS stage 4 disease orINRGSS stage M disease

3. Age >18 months at the time of enrolment into this study

4. Life expectancy of greater than 3 months

5. Performance Status 5.1. Karnofsky > 50% (for patients > 12 years of age) 5.2. Lansky > 50% (for patients ≤ 12 years of age)

6. Prior treatment 6.1. Two-week washout from any prior treatment 6.2. Patients musthave recovery of hematological toxicity following previous therapy 6.3. Adequaterecovery from major surgery prior to receiving study treatment

7. 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 twomonths prior to registration 7.2. 123I-mIBG scintigraphy to be performed within twomonths prior to registration 7.3. CT or MRI of the primary tumor and bulkymetastatic sites within two months prior to registration

8. Laboratory requirements to be performed within 7 days prior to commencing trialtreatment 8.1. Hematology: 8.1.1. Hemoglobin, If Hb is <120 g/L then patient willreceive a blood transfusion prior to commencing trial treatment 8.1.2. Absoluteneutrophil 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 asinulin, 51Cr-EDTA, 99mTc-DTPA or iohexol clearance and performed within 2 monthsprior to registration 8.2.7. Urinary catecholamine metabolites measured within 2months prior to registration

9. 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 toregistration

10. Written informed consent from patient and/or parent(s) or legal guardian(s) inaccordance with national regulations, prior to registration or any trial-relatedscreening procedures

Exclusion Criteria:

1. Not fit enough to undergo proposed study treatment, as assessed by national PI,considering precautions defined in the latest version of the 177Lutetium-DOTATATESmPC.

2. Pregnant or lactating patient

3. Concurrent treatment with any anti-tumor agents

4. Prior treatment with other radiolabeled somatostatin analogues

5. Hypersensitivity to any component of the investigational drug 177Lutetium-DOTATATE

6. Treatment with long-acting somatostatin analogues within 30 days, or withshort-acting somatostatin analogues within 24 hours prior the administration of 177Lutetium-DOTATATE