177Lu-DOTATATE treatment for children with high-risk neuroblastoma

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

This study is testing a new treatment called 177Lu-DOTATATE to see if it can help children with high-risk neuroblastoma that has come back or worsened.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Months and up
• Sex: All
• Sponsor: Karolinska University Hospital (Academic / other)
• Drugs / interventions: radiation
• Locations: 5 sites (Copenhagen, Copenhagen and 4 other locations)
• Trial ID: NCT04903899 on ClinicalTrials.gov

What this trial studies

The LuDO-N Trial is a multi-centre phase II clinical trial investigating the efficacy of 177Lu-DOTATATE in treating recurrent or relapsed high-risk neuroblastoma in children. This trial employs an intensified dosing schedule, administering two doses over a two-week period to maximize treatment effectiveness against this aggressive cancer. Patients will be monitored for treatment response at one and four months post-treatment, with additional assessments of survival rates and treatment-related toxicity. The study also aims to correlate tumor dosimetry and somatostatin receptor expression with treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are children over 18 months old with histologically confirmed high-risk neuroblastoma that is either relapsed or refractory.

Not a fit: Patients with low-risk neuroblastoma or those who do not meet the eligibility criteria, such as insufficient recovery from prior treatments, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for children with high-risk neuroblastoma, potentially leading to better survival rates.

How similar studies have performed: Previous studies using similar approaches have shown promise, indicating that this method may be a viable option for treating high-risk neuroblastoma.

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

Where this trial is running

Copenhagen, Copenhagen and 4 other locations

• Rigshospitalet — Copenhagen, Copenhagen, Denmark (Recruiting)
• Vilnius University Hospital — Vilnius, Vilnius County, Lithuania (Recruiting)
• Princess Maxima Center for Pediatric Oncology — Utrecht, Utrecht, Netherlands (Recruiting)
• Oslo University Hospital, Rikshospitalet — Oslo, Oslo, Norway (Recruiting)
• Karolinska University Hospital — Stockholm, Stockholm County, Sweden (Recruiting)

Study contacts

• Study coordinator: Jakob Stenman, MD PhD

Conditions Neuroblastoma Recurrent; Neuroblastoma