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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

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

Exclusion Criteria

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, 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To confirm the dose and assess response to single agent 177Lutetium-DOTATATE treatment in patients with relapsed or refractory high-risk neuroblastoma;Secondary Objective: To assess long term survival and response, To assess treatment-related toxicity;Primary end point(s): Response by the Revised International Neuroblastoma Response Criteria (INRC) at 1 month after the completion of therapy

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Response based on 68Ga-DOTATOC PET/CT imaging at 1 and 4 months after completion of therapy in measurable target lesions;Secondary end point(s):Response based on 123I-mIBG SPECT/CT imaging (when available) at 1 and 4 months after completion of therapy in measurable target lesions;Secondary end point(s):Response by the Revised INRC criteria at 4 months after the completion of therapy;Secondary end point(s):Progression free survival (PFS);Secondary end point(s):Overall survival (OS);Secondary end point(s):Hematological and renal toxicity according to CTCAE 5.0