Jennifer E Gains1, Veronica Moroz2, Matthew D Aldridge1,3, Simon Wan3, Keith Wheatley2, Jennifer Laidler2, Connie Peet1, Jamshed B Bomanji3, Mark N Gaze4. 1. Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK. 2. Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. 3. Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK. 4. Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK. mgaze@nhs.net.
Abstract
PURPOSE: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma. METHODS: Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg-1 per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastoma Response Criteria (primary outcome), progression-free survival (PFS), and overall survival (OS). RESULTS: The trial recruited 21 patients; eight received the planned four courses. There was dose-limiting haematologic toxicity in one case, but no other significant haematologic or renal toxicities. None of 14 evaluable patients had an objective response at 1 month after completion of treatment (Wilson 90% CI 0.0, 0.16; and 95% CI is 0.0, 0.22). The trial did not therefore proceed to the second stage. The median PFS was 2.96 months (95% CI 1.71, 7.66), and the median OS was 13.0 months (95% CI 2.99, 21.52). CONCLUSION: In the absence of any objective responses, the use of LuDO as a single agent at the dose schedule used in this study is not recommended for the treatment of neuroblastoma. There are several reasons why this treatment schedule may not have resulted in objective responses, and as other studies do show benefit, the treatment should not be regarded as being of no value. Further trials designed to overcome this schedule's limitations are required. TRIAL REGISTRATION: ISRCTN98918118; URL: https://www.isrctn.com/search?q=98918118.
PURPOSE: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma. METHODS:Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg-1 per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastoma Response Criteria (primary outcome), progression-free survival (PFS), and overall survival (OS). RESULTS: The trial recruited 21 patients; eight received the planned four courses. There was dose-limiting haematologic toxicity in one case, but no other significant haematologic or renal toxicities. None of 14 evaluable patients had an objective response at 1 month after completion of treatment (Wilson 90% CI 0.0, 0.16; and 95% CI is 0.0, 0.22). The trial did not therefore proceed to the second stage. The median PFS was 2.96 months (95% CI 1.71, 7.66), and the median OS was 13.0 months (95% CI 2.99, 21.52). CONCLUSION: In the absence of any objective responses, the use of LuDO as a single agent at the dose schedule used in this study is not recommended for the treatment of neuroblastoma. There are several reasons why this treatment schedule may not have resulted in objective responses, and as other studies do show benefit, the treatment should not be regarded as being of no value. Further trials designed to overcome this schedule's limitations are required. TRIAL REGISTRATION: ISRCTN98918118; URL: https://www.isrctn.com/search?q=98918118.
Authors: Fredrik Sundquist; 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; Lars Hjorth; Per Kogner; Dan Granberg; Mark Gaze; Jakob Stenman Journal: Front Pediatr Date: 2022-03-10 Impact factor: 3.418
Authors: Javian C Malcolm; Nadia Falzone; Jennifer E Gains; Matthew D Aldridge; David Mirando; Boon Q Lee; Mark N Gaze; Katherine A Vallis Journal: EJNMMI Phys Date: 2022-03-28
Authors: Sara Lundsten; Hanna Berglund; Preeti Jha; Cecilia Krona; Mehran Hariri; Sven Nelander; David P Lane; Marika Nestor Journal: Biomolecules Date: 2021-11-15