A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma LuDO-N

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Neoplasms [C04]

Trial duration

20 Feb 2026 → ongoing

Decision date (initial)

2023-05-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503684-42-00

EudraCT number

2020-004445-36

ClinicalTrials.gov

NCT04903899

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To confirm the dose and assess response to single agent 177Lutetium-DOTATATE treatment in patients with relapsed or refractory high-risk neuroblastoma

Secondary objectives 2

1. To assess long term survival and response
2. To assess treatment-related toxicity

Conditions and MedDRA coding

Neuroblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 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 7

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. 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
7. Hydronephrosis in either kidney on baseline MRI or CT; patients can still be eligible for inclusion if urinary tract obstruction can be ruled out by renography.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response by the Revised International Neuroblastoma Response Criteria (INRC) at 1 month after the completion of therapy

Secondary endpoints 6

1. Response based on 68Ga-DOTATOC PET/CT imaging at 1 and 4 months after completion of therapy in measurable target lesions
2. Response based on 123I-mIBG SPECT/CT imaging (when available) at 1 and 4 months after completion of therapy in measurable target lesions
3. Response by the Revised INRC criteria at 4 months after the completion of therapy
4. Progression free survival (PFS)
5. Overall survival (OS)
6. Hematological and renal toxicity according to CTCAE 5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Jakob Stenman

Public contact point

Organisation

Karolinska University Hospital

Contact name

Jakob Stenman

Third parties 1

Locations

6 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 6 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 84 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications