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

NCT ID: NCT04903899

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-19
• Study Completion Date: 2031-05-20

Brief 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.

Conditions

Neuroblastoma Recurrent; Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

177Lu-DOTATATE

A total of two doses of 177Lu-DOTATATE will be administered intravenously. The minimum time between treatments is 2 weeks.

Group Type: EXPERIMENTAL

177Lu-DOTATATE

Intervention Type: COMBINATION_PRODUCT

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.

Interventions

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.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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 > 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

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 registration

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 177Lutetium-DOTATATE 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 177Lutetium-DOTATATE

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

• Minimum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advanced Accelerator Applications

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Jakob Stenman

OTHER

Sponsor Role: lead

Responsible Party

Jakob Stenman

Consultant Pediatric Surgeon, Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jakob Stenman, MD PhD

Role: STUDY_CHAIR

Karolinska University Hospital

Locations

Rigshospitalet

Copenhagen, Copenhagen, Denmark

Site Status: RECRUITING

Vilnius University Hospital

Vilnius, Vilnius County, Lithuania

Site Status: RECRUITING

Princess Maxima Center for Pediatric Oncology

Utrecht, Utrecht, Netherlands

Site Status: RECRUITING

Oslo University Hospital, Rikshospitalet

Oslo, Oslo County, Norway

Site Status: RECRUITING

Karolinska University Hospital

Stockholm, Stockholm County, Sweden

Site Status: RECRUITING

Countries

Denmark; Lithuania; Netherlands; Norway; Sweden

Central Contacts

Jakob Stenman, MD PhD

Role: CONTACT

jakob.stenman@sll.se

(0)51770000 ext. 46

Kleopatra Georgantzi, MD

Role: CONTACT

kleopatra.georgantzi@sll.se

(0)51770000 ext. 46

Facility Contacts

Jesper S Brok, MD PhD

Role: primary

jesper.sune.brok@regionh.dk

Jelena Rascon, MD PhD

Role: primary

jelena.rascon@gmail.com

Max M van Noesel, MD PhD

Role: primary

M.M.vanNoesel@prinsesmaximacentrum.nl

Kirsten Brunsvig Jarvis, MD

Role: primary

kirjar@ous-hf.no

Kleopatra Georgantzi, MD

Role: primary

kleopatra.georgantzi@sll.se

Jakob Stenman, MD PhD

Role: backup

jakob.stenman@sll.se

References

Sundquist F, Georgantzi K, Jarvis KB, Brok J, Koskenvuo M, Rascon J, van Noesel M, Gryback P, Nilsson J, Braat A, Sundin M, Wessman S, Herold N, Hjorth L, Kogner P, Granberg D, Gaze M, Stenman J. A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma-LuDO-N. Front Pediatr. 2022 Mar 10;10:836230. doi: 10.3389/fped.2022.836230. eCollection 2022.

Reference Type: DERIVED

PMID: 35359899 (View on PubMed)

Other Identifiers

LuDO-N

Identifier Type: -

Identifier Source: org_study_id