[177Lu]Lu-DOTATATE Molecular Radiotherapy During Induction Chemotherapy for First-Line Stage 4 High-Risk Neuroblastoma in South African Children: Protocol for a Phase 1 Randomized Controlled Trial (LuDO-SA Trial)

Jaques van Heerden; Mariana Kruger; Kershinee Reddy; Anel van Zyl; James Warwick; Celeste Burger; Tumelo Moalosi; Christoffel van Reenen; Alan Davidson; Khanyisile Hlongwa; Daniella Violante; Nanette Bruwer; Gita Naidu; Biance Rowe; Lizette Louw; Bronwin van Wyk; Mariza Vorster; Thokozani Mkhize; Anita Brink

doi:10.2196/93547

[177Lu]Lu-DOTATATE Molecular Radiotherapy During Induction Chemotherapy for First-Line Stage 4 High-Risk Neuroblastoma in South African Children: Protocol for a Phase 1 Randomized | ResearchHub

Abstract

Abstract Background In South Africa, the metastatic response rate for stage 4 high-risk neuroblastoma (HR-NB) to induction chemotherapy is lower than that of similar regimens in well-resourced settings. Augmenting current induction chemotherapy regimens with molecular radiotherapy, without increasing toxicity, is an attractive systemic treatment in radioisotope-avid tumors, especially in a resource-limited setting where stem cell transplantation and immunotherapy are unavailable and costly. Clinical trials of [ 177 Lu]Lutetium DOTATATE ([ 177 Lu]Lu-DOTATATE) have primarily focused on refractory or relapsed HR-NB, with disappointing results. This study evaluates the feasibility and dose-limiting toxicity grading of adding a single dose of [ 177 Lu]Lu-DOTATATE to induction chemotherapy in achieving metastatic remission rates. Objective The aim of the proof-of-concept, open-label study is to evaluate the safety and efficacy of induction [ 177 Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) on postinduction response rate in children diagnosed with HR-NB. The primary objectives are to evaluate the dose-limiting toxicity profile of participants treated with induction [ 177 Lu]Lu-DOTATATE PRRT in conjunction with standard induction chemotherapy; to evaluate the dosimetry in South African patients receiving induction [ 177 Lu]Lu-DOTATATE PRRT; and to evaluate the feasibility related to resources in patients treated with induction [ 177 Lu]Lu-DOTATATE PRRT in conjunction with standard induction chemotherapy. The secondary objective is to determine the postinduction metastatic response rate in patients diagnosed with HR-NB after receiving induction [ 177 Lu]Lu-DOTATATE PRRT in conjunction with standard induction chemotherapy. Methods The LuDO-SA trial is a phase 1, open-label, multicenter, 2-arm, randomized controlled clinical trial. Children aged 18 months to 18 years are eligible. The experimental arm, consisting of a single dose of [ 177 Lu]Lu-DOTATATE after cycle 1 of OJEC (vincristine, carboplatin, etoposide, and cyclophosphamide) and OPEC (vincristine, cisplatin, etoposide, and cyclophosphamide) chemotherapy, will be compared to the standard arm of OJEC and OPEC chemotherapy. The postinduction metastatic response rate is based on the International Neuroblastoma Response Criteria (INRC). The statistical analysis will be descriptive. The Fisher exact test will be used to evaluate the significance of end-of-trial outcomes. Results The trial received institutional ethics approval from 4 South African universities in 2022 and SAHPRA (South African Health Products Regulatory Authority) regulatory approval. The trial, funded by Kinderkankerfonds vzw and the UZA Foundation, commenced recruitment in January 2023. As of July 2026, a total of 15 patients have been enrolled across 4 academic hospital sites. Recruitment is projected to be completed by June 2027, with results expected to be published in December 2027. Conclusions In this paper, we present the protocol of the LuDO-SA trial. The rationale and design of the trial in a resource-limited setting and its use in first-line regimens are discussed, and the current status of international [ 177 Lu]Lu-DOTATATE molecular radiotherapy trials is summarized.

External reference records

Challenges for paediatric oncology in Africa

10.1016/s1470-2045(12)70569-7

SIOP-PODC adapted risk stratification and treatment guidelines: recommendations for neuroblastoma in low- and middle-income settings

10.1002/pbc.25501

Overall survival for neuroblastoma in South Africa between 2000 and 2014

10.1002/pbc.27944

Factors associated with recurrence and survival length following relapse in patients with neuroblastoma

10.1038/bjc.2016.302

The importance of local control management in high-risk neuroblastoma in South Africa

10.1007/s00383-020-04627-x

Predictors of differential response to induction therapy in high-risk neuroblastoma: a report from the Children’s Oncology Group (COG)

10.1016/j.ejca.2019.02.003

Advances in anti-GD2 immunotherapy for treatment of high-risk neuroblastoma

10.1097/mph.0000000000001369

Topotecan-vincristine-doxorubicin in stage 4 high-risk neuroblastoma patients failing to achieve a complete metastatic response to rapid COJEC: a SIOPEN study

10.4143/crt.2016.511

Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial

10.1016/s1470-2045(18)30578-3

The radiobiology of human neuroblastoma

10.1016/s0167-8140(85)80029-3

Nuclear medicine imaging in neuroblastoma: current status and new developments

10.3390/jpm11040270

177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma

10.2967/jnumed.110.085100

Toxicity of upfront ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis

10.1007/s00259-013-2510-z

Radiolabeled metaiodobenzylguanidine for the treatment of neuroblastoma

10.1016/j.nucmedbio.2008.05.002

Molybdenum-99 production in South Africa

10.1007/bf01249633

Unresolved referenced work

Kept as external metadata until matched

Initial experience with gallium-68 DOTA-Octreotate PET/CT and peptide receptor radionuclide therapy for pediatric patients with refractory metastatic neuroblastoma

10.1097/mph.0000000000000411

Paediatric molecular radiotherapy: challenges and opportunities

10.1016/j.clon.2020.11.007

A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma

10.1007/s00259-020-04741-x

Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [Lu]Lu-DOTATATE

10.1186/s40658-022-00436-4

Feasibility and therapeutic potential of combined peptide receptor radionuclide therapy with intensive chemotherapy for pediatric patients with relapsed or refractory metastatic neuroblastoma

10.1097/rlu.0000000000003577

Role of F-AlF-NOTATATE PET/CT in selecting pediatric neuroblastoma candidates for Lu-DOTATATE peptide receptor radionuclide therapy

10.3389/fmed.2025.1615136

A phase II trial of a personalized, dose-intense administration schedule of lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma-LuDO-N

10.3389/fped.2022.836230

Review: the role of radiolabeled DOTA-conjugated peptides for imaging and treatment of childhood neuroblastoma

10.2174/1874471011666171215093112

Phase 3 trial of Lu-Dotatate for midgut neuroendocrine tumors

10.1056/nejmoa1607427

Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study

10.1007/s00259-020-04873-0

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients

10.1016/j.ejca.2016.12.013

Individualized dosimetry to guide LuTATE therapy in pediatric neuroblastoma

10.1055/s-0045-1812305

Validation of Postinduction Curie Scores in High-Risk Neuroblastoma: a children’s oncology group and SIOPEN group report on SIOPEN/HR-NBL1

10.2967/jnumed.117.195883

Unresolved referenced work

Kept as external metadata until matched

What makes clinical research in developing countries ethical? The benchmarks of ethical research

10.1086/381709

Unresolved referenced work

Kept as external metadata until matched

Additional external references

No additional external references are available.

[177Lu]Lu-DOTATATE Molecular Radiotherapy During Induction Chemotherapy for First-Line Stage 4 High-Risk Neuroblastoma in South African Children: Protocol for a Phase 1 Randomized Controlled Trial (LuDO-SA Trial)

Referenced works

Cited by

External reference records

Additional external references