Clinical Trial · NCT04903899

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

Overview

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.

Sponsor

Karolinska University Hospital

Phase

Phase 2

Contacts

Kleopatra Georgantzi, MD (CONTACT)

kleopatra.georgantzi@sll.se

(0)51770000

Jakob Stenman, MD PhD (STUDY_CHAIR)

Jakob Stenman, MD PhD (CONTACT)

jakob.stenman@sll.se

(0)51770000

ClinicalTrials.gov

NCT04903899

Drug / Compound

DOTATATE

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

DOTATATE

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

Eligibility

Inclusion

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 and performed within 2 months prior to registration 8.2.7. Urinary catecholamine metabolites measured within 2 months prior to registration
Life expectancy of greater than 3 months
Relapsed or primary refractory high-risk neuroblastoma: INSS stage 4 disease or INRGSS stage M disease
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
Pathology 1.1. Histologically confirmed diagnosis of neuroblastoma 1.2. Immunohistochemical staining for somatostatin receptors (SSTR) performed from primary tumor tissue when available
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
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

Pregnant or lactating patient
Treatment with long-acting somatostatin analogues within 30 days, or with short-acting somatostatin analogues within 24 hours prior the administration of 177Lutetium-DOTATATE
Concurrent treatment with any anti-tumor agents
Hypersensitivity to any component of the investigational drug 177Lutetium-DOTATATE
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.
Prior treatment with other radiolabeled somatostatin analogues