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177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-risk Neuroblastoma (LuDO-N)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04903899
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : May 27, 2021
Advanced Accelerator Applications
Information provided by (Responsible Party):
Jakob Stenman, Karolinska University Hospital

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Recurrent Neuroblastoma Combination Product: 177Lu-DOTATATE Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-risk Neuroblastoma
Actual Study Start Date : May 19, 2021
Estimated Primary Completion Date : May 20, 2026
Estimated Study Completion Date : May 20, 2031

Arm Intervention/treatment
Experimental: 177Lu-DOTATATE
A total of two doses of 177Lu-DOTATATE will be administered intravenously. The minimum time between treatments is 2 weeks.
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.

Primary Outcome Measures :
  1. Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) [ Time Frame: 1 months following end of treatment ]

Secondary Outcome Measures :
  1. Number and severity of treatment-related adverse events [ Time Frame: Up to 5 years after end of treatment ]
  2. Treatment response assessed in accordance with the Revised International Neuroblastoma Response Criteria (INRC) [ Time Frame: 4 months following end of treatment ]
  3. Progression-free survival [ Time Frame: Time from registration to progression or death, up to 5 years following end of treatment ]
    Time to progress or death, whichever occurs first

  4. Overall survival [ Time Frame: Time from registration to the the date of death, up to 5 years following end of treatment ]

Other Outcome Measures:
  1. Tumour dosimetry: absorbed dose per administration of 177Lu-DOTATATE [ Time Frame: At every administered dose of 177Lu-DOTATATE throughout the trial treatment phase (5 years) ]
    Measured by SPECT/CT

  2. Correlation of expression of Somatostatin Receptor-2 (SSTR-2) to uptake on 68Ga-DOTATOC PET/CT [ Time Frame: Throughout the trial treatment phase (5 years) ]
    SSTR-2 expression in the histology samples from primary surgery measured by immunohistochemistry.

  3. Uptake on 68Ga-DOTATOC PET/CT [ Time Frame: At end of treatment, and 1 and 4 months after end of treatment. ]
    Measured by SUVmax (maximum standardized uptake value)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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®

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04903899

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Contact: Jakob Stenman, MD PhD (0)51770000 ext 46
Contact: Kleopatra Georgantzi, MD (0)51770000 ext 46

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Rigshospitalet Not yet recruiting
Copenhagen, Denmark, DK-2100
Contact: Jesper S Brok, MD PhD   
Principal Investigator: Jesper S Brok, MD PhD         
New Children's Hospital, Helsinki University Hospital Not yet recruiting
Helsinki, HUS, Finland, FI-00029
Contact: Minna Koskenvuo, MD PhD   
Principal Investigator: Minna Koskenvuo, MD PhD         
Vilnius University Hospital Not yet recruiting
Vilnius, Lithuania, LT-08406
Contact: Jelena Rascon, MD PhD   
Principal Investigator: Jelena Rascon, MD PhD         
Princess Maxima Center for Pediatric Oncology Not yet recruiting
Utrecht, Netherlands, NL-3584
Contact: Max M van Noesel, MD PhD   
Principal Investigator: Max M van Noesel, MD PhD         
Oslo University Hospital, Rikshospitalet Not yet recruiting
Oslo, Norway, NO-0372
Contact: Kirsten Brunsvig Jarvis, MD   
Principal Investigator: Kirsten Brunsvig Jarvis, MD         
Karolinska University Hospital Recruiting
Stockholm, Sweden, SE-171 76
Contact: Kleopatra Georgantzi, MD   
Contact: Jakob Stenman, MD PhD   
Principal Investigator: Kleopatra Georgantzi, MD         
Sponsors and Collaborators
Jakob Stenman
Advanced Accelerator Applications
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Study Chair: Jakob Stenman, MD PhD Karolinska University Hospital
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Responsible Party: Jakob Stenman, Consultant Pediatric Surgeon, Associate Professor, Karolinska University Hospital Identifier: NCT04903899    
Other Study ID Numbers: LuDO-N
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue