[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)

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.