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

Phase 1

Conditions: Primary refractory or relapsed high-risk neuroblastoma.
MedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-004445-36-DK

Lead Sponsor: Karolinska University Hospital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 25

Inclusion Criteria

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

2. Relapsed or primary refractory high-risk neuroblastoma: INSS stage 4 disease or INRGSS 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 must have recovery of hematological toxicity following previous therapy 6.3. Adequate recovery 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 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

8. 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 > 100 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 and performed within 2 months prior to registration
8.2.7. Urinary catecholamine metabolites measured within 2 months 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 to registering

10. 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 25
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 Lutathera SmPC

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 Lutathera®

6. Treatment with long-acting somatostatin analogues within 30 days prior the administration of Lutathera®

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<br>- To assess treatment-related toxicity<br>- To correlate tumour dosimetry with response<br>- To correlate somatostatin type 2 receptor (SSTR-2) expression with 68Ga-DOTATOC PET/CT<br>uptake<br>- To correlate the uptake on 68Ga-DOTATOC PET/CT with response to 177Lu-DOTATATE therapy;Primary end point(s): Response by the Revised International Neuroblastoma Response Criteria (INRC).;Timepoint(s) of evaluation of this end point: At 1 month after the completion of therapy.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1 Response by the Revised INRC criteria<br>2 Progression free survival (PFS)<br>3 Overall survival (OS)<br>4 Hematological and renal toxicity according to CTCAE 5.0<br>5 Response assessed as a lesional analysis of the relationship between<br>absorbed dose recieved in each measurable leasion and response in the<br>lesion.;Timepoint(s) of evaluation of this end point: 1 At 4 months after the completion of therapy.<br>2 From registration until objective tumour progression or death or to date of censoring for patients who do not experience the event during trial follow-up.<br>3 From registration into the trial until date of death from any cause or to date of censoring for patients who do not experience the event during trial follow-up.<br>4 From registration until the 4 months' follow-up.<br>5 At 1 month after the completion of therapy.