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

Neuroblastoma Clinical Trial

— LuDO-N  

Official title:

A Phase II Trial of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-risk Neuroblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04903899
• Other study ID #: LuDO-N
• Status: Recruiting
• Phase: Phase 2
• Start date: May 19, 2021
• Est. completion date: May 20, 2031

Study information

• Verified date: March 2024
• Source: Karolinska University Hospital
• Contact: Jakob Stenman, MD PhD
• Phone: (0)51770000
• Email: jakob.stenman[@]sll.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: May 20, 2031
• Est. primary completion date: May 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 18 Years

Eligibility

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: International Neuroblastoma Staging System (INSS) stage 4 disease or International Neuroblastoma Risk Group Staging System (INRGSS) stage M disease

3. Age >18 months and < 18 years of age 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 4 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

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. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient or legal guardian before registration in the trial

6. Hypersensitivity to any component of the investigational drug Lutathera®

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

Related Conditions & MeSH terms

• Neuroblastoma
• Neuroblastoma Recurrent

Intervention

Combination Product:
• 177Lu-DOTATATE
A weight-based activity of 200 MBq kg-1 will be used for the first dose. The activity of the second dose will be calculated based on whole body activity scans as well as SPECT CT scans to determine the absorbed kidney dose. The aim is to administer 177Lu-DOTATATE corresponding to a whole-body dose of 1,2 Gy, with a cumulative whole-body dose of about 2,4 Gy over two courses, and not exceeding a cumulative renal dose of 23 Gy, in order to avoid renal toxicity.

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
Lithuania	Vilnius University Hospital	Vilnius
Netherlands	Princess Maxima Center for Pediatric Oncology	Utrecht
Norway	Oslo University Hospital, Rikshospitalet	Oslo
Sweden	Karolinska University Hospital	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Jakob Stenman	Advanced Accelerator Applications, Novartis

Countries where clinical trial is conducted

Denmark,  Lithuania,  Netherlands,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumour dosimetry: absorbed dose per administration of 177Lu-DOTATATE	Measured by SPECT/CT	At every administered dose of 177Lu-DOTATATE throughout the trial treatment phase (5 years)
Other	Correlation of expression of Somatostatin Receptor-2 (SSTR-2) to uptake on 68Ga-DOTATOC PET/CT	SSTR-2 expression in the histology samples from primary surgery measured by immunohistochemistry.	Throughout the trial treatment phase (5 years)
Other	Uptake on 68Ga-DOTATOC PET/CT	Measured by SUVmax (maximum standardized uptake value)	At end of treatment, and 1 and 4 months after end of treatment.
Primary	Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) - 1 months after End of Treatment	Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC)	1 months following end of treatment
Secondary	Number and severity of treatment-related adverse events	Number and severity of treatment-related adverse events	Up to 5 years after end of treatment
Secondary	Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) - 4 months after End of Treatment	Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC)	4 months following end of treatment
Secondary	Progression-free survival	Time to progress or death, whichever occurs first	Time from registration to progression or death, up to 5 years following end of treatment
Secondary	Overall survival - up to 5 years after End of Treatment	Overall survival	Time from registration to the the date of death, up to 5 years following end of treatment