A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N
BackgroundHalf 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 17...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.836230/full |
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| author | Fredrik Sundquist Kleopatra Georgantzi Kleopatra Georgantzi Kirsten Brunsvig Jarvis Jesper Brok Minna Koskenvuo Jelena Rascon Max van Noesel Per Grybäck Joachim Nilsson Arthur Braat Mikael Sundin Sandra Wessman Nikolas Herold Nikolas Herold Lars Hjorth Per Kogner Dan Granberg Mark Gaze Jakob Stenman Jakob Stenman |
| author_facet | Fredrik Sundquist Kleopatra Georgantzi Kleopatra Georgantzi Kirsten Brunsvig Jarvis Jesper Brok Minna Koskenvuo Jelena Rascon Max van Noesel Per Grybäck Joachim Nilsson Arthur Braat Mikael Sundin Sandra Wessman Nikolas Herold Nikolas Herold Lars Hjorth Per Kogner Dan Granberg Mark Gaze Jakob Stenman Jakob Stenman |
| author_sort | Fredrik Sundquist |
| collection | DOAJ |
| description | BackgroundHalf 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.MethodsThe 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.ResultsThe 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.DiscussionIn 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. |
| first_indexed | 2024-12-13T09:38:14Z |
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| last_indexed | 2024-12-13T09:38:14Z |
| publishDate | 2022-03-01 |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-4eefac4b9e3e4eff9c397d89389de19b2022-12-21T23:52:16ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-03-011010.3389/fped.2022.836230836230A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-NFredrik Sundquist0Kleopatra Georgantzi1Kleopatra Georgantzi2Kirsten Brunsvig Jarvis3Jesper Brok4Minna Koskenvuo5Jelena Rascon6Max van Noesel7Per Grybäck8Joachim Nilsson9Arthur Braat10Mikael Sundin11Sandra Wessman12Nikolas Herold13Nikolas Herold14Lars Hjorth15Per Kogner16Dan Granberg17Mark Gaze18Jakob Stenman19Jakob Stenman20Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SwedenDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, SwedenPediatric Oncology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, SwedenDepartment of Paediatric Haematology and Oncology, Oslo University Hospital, Rikshospitalet, Oslo, NorwayDepartment of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, DenmarkHelsinki University Central Hospital, University of Helsinki, Helsinki, FinlandCenter for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius, LithuaniaSolid Tumor Department, Princess Máxima Center for Pediatric Oncology, Utrecht, NetherlandsDepartment of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Nuclear Medicine, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands0Division of Pediatrics, Department of Pediatric Hematology, Immunology and HCT, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden1Department of Pathology, Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, SwedenPediatric Oncology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden2Department of Clinical Sciences Lund, Paediatrics, Lund University, Skane University Hospital, Lund, SwedenDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden3Department of Breast, Endocrine Tumors and Sarcomas, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden4Department of Oncology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden5Department of Pediatric Surgery, Karolinska University Hospital, Stockholm, SwedenBackgroundHalf 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.MethodsThe 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.ResultsThe 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.DiscussionIn 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.https://www.frontiersin.org/articles/10.3389/fped.2022.836230/fullneuroblastomarelapserefractory177Lu-DOTATATEPRRTradiopharmaceutical |
| spellingShingle | Fredrik Sundquist Kleopatra Georgantzi Kleopatra Georgantzi Kirsten Brunsvig Jarvis Jesper Brok Minna Koskenvuo Jelena Rascon Max van Noesel Per Grybäck Joachim Nilsson Arthur Braat Mikael Sundin Sandra Wessman Nikolas Herold Nikolas Herold Lars Hjorth Per Kogner Dan Granberg Mark Gaze Jakob Stenman Jakob Stenman A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N Frontiers in Pediatrics neuroblastoma relapse refractory 177Lu-DOTATATE PRRT radiopharmaceutical |
| title | A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N |
| title_full | A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N |
| title_fullStr | A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N |
| title_full_unstemmed | A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N |
| title_short | A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N |
| title_sort | phase ii trial of a personalized dose intense administration schedule of 177lutetium dotatate in children with primary refractory or relapsed high risk neuroblastoma ludo n |
| topic | neuroblastoma relapse refractory 177Lu-DOTATATE PRRT radiopharmaceutical |
| url | https://www.frontiersin.org/articles/10.3389/fped.2022.836230/full |
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