A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177 Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N

Frontiers in Pediatrics

article

Fredrik Sundquist¹  Kleopatra Georgantzi¹  Kirsten Brunsvig Jarvis³  Jesper Brok⁴  Minna Koskenvuo⁵  Jelena Rascon⁶  Max van Noesel⁷  Per Grybäck⁸  Joachim Nilsson⁸  Arthur Braat⁹  Mikael Sundin^1,10  Sandra Wessman^1,11  Nikolas Herold¹  Lars Hjorth^1,12  Per Kogner¹  Dan Granberg^1,13  Mark Gaze^1,14  Jakob Stenman¹ 

[1] Department of Women's and Children's Health, Karolinska Institutet;Pediatric Oncology, Astrid Lindgren Children's Hospital, Karolinska University Hospital;Department of Paediatric Haematology and Oncology, Oslo University Hospital, Rikshospitalet;Department of Paediatrics and Adolescent Medicine, Rigshospitalet;Helsinki University Central Hospital, University of Helsinki;Center for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos;Solid Tumor Department, Princess Máxima Center for Pediatric Oncology;Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital;Department of Nuclear Medicine, Princess Máxima Center for Pediatric Oncology;Division of Pediatrics, Department of Pediatric Hematology, Immunology and HCT, Department of Clinical Science, Intervention and Technology ,(CLINTEC), Karolinska University Hospital, Karolinska Institute;Department of Pathology, Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet;Department of Clinical Sciences Lund, Paediatrics, Lund University, Skane University Hospital;Department of Breast, Endocrine Tumors and Sarcomas, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet;Department of Oncology, University College London Hospitals NHS Foundation Trust;Department of Pediatric Surgery, Karolinska University Hospital

关键词: neuroblastoma;    relapse;    refractory;    177 Lu-DOTATATE;    PRRT;    radiopharmaceutical;    therapy;    high-risk;   

DOI  :  10.3389/fped.2022.836230

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Half the children with high-risk neuroblastoma die with widespread metastases. Molecular radiotherapy is an attractive systemic treatment for this relatively radiosensitive tumor. 131I-mIBG is the most widely used form in current use, but is not universally effective. Clinical trials of 177Lutetium DOTATATE have so far had disappointing results, possibly because the administered activity was too low, and the courses were spread over too long a period of time, for a rapidly proliferating tumor. We have devised an alternative administration schedule to overcome these limitations. This involves two high-activity administrations of single agent 177Lu-DOTATATE given 2 weeks apart, prescribed as a personalized whole body radiation absorbed dose, rather than a fixed administered activity. “A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma - LuDO-N” (EudraCT No: 2020-004445-36, ClinicalTrials.gov Identifier: NCT04903899) evaluates this new dosing schedule.Methods: The LuDO-N trial is a phase II, open label, multi-center, single arm, two stage design clinical trial. Children aged 18 months to 18 years are eligible. The trial is conducted by the Nordic Society for Pediatric Hematology and Oncology (NOPHO) and it has been endorsed by SIOPEN (https://www.siopen.net). The Karolinska University Hospital, is the sponsor of the LuDO-N trial, which is conducted in collaboration with Advanced Accelerator Applications, a Novartis company. All Scandinavian countries, Lithuania and the Netherlands participate in the trial and the UK has voiced an interest in joining in 2022. Results: The pediatric use of the Investigational Medicinal Product (IMP) 177Lu-DOTATATE, as well as non-IMPs SomaKit TOC® ( 68Ga-DOTATOC) and LysaKare® amino acid solution for renal protection, have been approved for pediatric use, within the LuDO-N Trial by the European Medicines Agency (EMA). The trial is currently recruiting. Recruitment is estimated to be finalized within 3–5 years. Discussion: In this paper we present the protocol of the LuDO-N Trial. The rationale and design of the trial are discussed in relation to other ongoing, or planned trials with similar objectives. Further, we discuss the rapid development of targeted radiopharmaceutical therapy and the future perspectives for developing novel therapies for high-risk neuroblastoma and other pediatric solid tumors.

【 授权许可】

CC BY