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

NCT04903899 | Recruiting Phase 2 DMC

• 1 other identifier: LuDO-N
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number and severity of treatment-related adverse events

  Up to 5 years after end of treatment

• Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) - 4 months after End of Treatment

  4 months following end of treatment

• Progression-free survival

  Time from registration to progression or death, up to 5 years following end of treatment

• Overall survival - up to 5 years after End of Treatment

  Time from registration to the the date of death, up to 5 years following end of treatment

Other Outcomes (3)

• Tumour dosimetry: absorbed dose per administration of 177Lu-DOTATATE

  At every administered dose of 177Lu-DOTATATE throughout the trial treatment phase (5 years)

• Correlation of expression of Somatostatin Receptor-2 (SSTR-2) to uptake on 68Ga-DOTATOC PET/CT

  Throughout the trial treatment phase (5 years)

• Uptake on 68Ga-DOTATOC PET/CT

  At end of treatment, and 1 and 4 months after end of treatment.

Study Arms (1)

177Lu-DOTATATE

EXPERIMENTAL

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

Combination Product: 177Lu-DOTATATE

Interventions

177Lu-DOTATATE 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.

177Lu-DOTATATE

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathology 1.1. Histologically confirmed diagnosis of neuroblastoma 1.2. Immunohistochemical staining for somatostatin receptors (SSTR) performed from primary tumor tissue when available
• 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 and performed within 2 months 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Jakob Stenman: lead
• Advanced Accelerator Applications: collaborator
• Novartis: collaborator

Study Sites (5)

Rigshospitalet

Copenhagen, Copenhagen, DK-2100, Denmark

RECRUITING

Vilnius University Hospital

Vilnius, Vilnius County, LT-08406, Lithuania

RECRUITING

Princess Maxima Center for Pediatric Oncology

Utrecht, Utrecht, NL-3584, Netherlands

RECRUITING

Oslo University Hospital, Rikshospitalet

Oslo, Oslo County, NO-0372, Norway

RECRUITING

Karolinska University Hospital

Stockholm, Stockholm County, SE-171 76, Sweden

RECRUITING

Related Publications (1)

• 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.

  PMID: 35359899 DERIVED

MeSH Terms

Conditions

Neuroblastoma

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Jakob Stenman, MD PhD

  Karolinska University Hospital

  STUDY CHAIR

Central Study Contacts

Jakob Stenman, MD PhD

CONTACT

(0)51770000; jakob.stenman@sll.se

Kleopatra Georgantzi, MD

CONTACT

(0)51770000; kleopatra.georgantzi@sll.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant Pediatric Surgeon, Associate Professor

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 27, 2021
• Study Start: May 19, 2021
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): May 20, 2031
• Last Updated: February 11, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); NL (1); DK (1); SE (1); LI (1)