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Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)

BACKGROUND: (68)Ga-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) positron emission tomography–CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT–CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation...

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Autores principales: Manoharan, Prakash, Lamarca, Angela, Navalkissoor, Shaunak, Calero, Jose, Chan, Pei San, Julyan, Peter, Sierra, Maribel, Caplin, Martyn, Valle, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078687/
https://www.ncbi.nlm.nih.gov/pubmed/32188715
http://dx.doi.org/10.1136/esmoopen-2019-000650
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author Manoharan, Prakash
Lamarca, Angela
Navalkissoor, Shaunak
Calero, Jose
Chan, Pei San
Julyan, Peter
Sierra, Maribel
Caplin, Martyn
Valle, Juan
author_facet Manoharan, Prakash
Lamarca, Angela
Navalkissoor, Shaunak
Calero, Jose
Chan, Pei San
Julyan, Peter
Sierra, Maribel
Caplin, Martyn
Valle, Juan
author_sort Manoharan, Prakash
collection PubMed
description BACKGROUND: (68)Ga-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) positron emission tomography–CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT–CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of (68)Ga-DOTATOC using a new ‘ready-to-use’ (68)Ga-DOTATOC formulation for injection has been developed ((68)Ga-DOTATOC (SomaKIT TOC)). OBJECTIVES: This study aimed to assess the safety and tolerability of (68)Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service. METHODS: A first-in-human phase I/II multicentre, open-label study of a single dose of (68)Ga-DOTATOC (SomaKIT TOC) 2 MBq/kg±10% (range 100–200 MBq) in patients with biopsy-proven grade 1–2 GEP-NETs. PET-CT was performed post injection. Patients were followed up for 28 days. We next implemented this new synthesis methodology in a clinical service assessed over 11 months. RESULTS: Twenty consenting patients were recruited; 14 males, 6 females; mean (SD) age 58 years (12); NET grade 1 (70%), grade 2 (30%); and 75% with stage IV disease. Twelve patients experienced at least one adverse event (AE) during the study with no grade 3–4 toxicities. Only four AEs were classified as possibly (headache (n=1; 4%), nausea (1; 4%)) or probably (dysgeusia (1; 4%), paraesthesia (1; 4%)) related to the study preparation. One hundred thirteen vials of (68)Ga-DOTATOC (SomaKIT TOC) were synthesised with the ‘kit’ over a period of 11 months for clinical utility. Only 2/113 vials (1.77%) were rejected. CONCLUSIONS: The new ready-to-use preparation of (68)Ga-DOTATOC (SomaKIT TOC) for injection was safe and well tolerated. This has led to the world’s first (EMA) licensed (68)Ga-DOTATOC (SomaKIT TOC) radiopharmaceutical for the utility of PET imaging in patients with NETs. This preparation can be robustly implemented into routine clinical practice.
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spelling pubmed-70786872020-03-23 Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) Manoharan, Prakash Lamarca, Angela Navalkissoor, Shaunak Calero, Jose Chan, Pei San Julyan, Peter Sierra, Maribel Caplin, Martyn Valle, Juan ESMO Open Original Research BACKGROUND: (68)Ga-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) positron emission tomography–CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT–CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of (68)Ga-DOTATOC using a new ‘ready-to-use’ (68)Ga-DOTATOC formulation for injection has been developed ((68)Ga-DOTATOC (SomaKIT TOC)). OBJECTIVES: This study aimed to assess the safety and tolerability of (68)Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service. METHODS: A first-in-human phase I/II multicentre, open-label study of a single dose of (68)Ga-DOTATOC (SomaKIT TOC) 2 MBq/kg±10% (range 100–200 MBq) in patients with biopsy-proven grade 1–2 GEP-NETs. PET-CT was performed post injection. Patients were followed up for 28 days. We next implemented this new synthesis methodology in a clinical service assessed over 11 months. RESULTS: Twenty consenting patients were recruited; 14 males, 6 females; mean (SD) age 58 years (12); NET grade 1 (70%), grade 2 (30%); and 75% with stage IV disease. Twelve patients experienced at least one adverse event (AE) during the study with no grade 3–4 toxicities. Only four AEs were classified as possibly (headache (n=1; 4%), nausea (1; 4%)) or probably (dysgeusia (1; 4%), paraesthesia (1; 4%)) related to the study preparation. One hundred thirteen vials of (68)Ga-DOTATOC (SomaKIT TOC) were synthesised with the ‘kit’ over a period of 11 months for clinical utility. Only 2/113 vials (1.77%) were rejected. CONCLUSIONS: The new ready-to-use preparation of (68)Ga-DOTATOC (SomaKIT TOC) for injection was safe and well tolerated. This has led to the world’s first (EMA) licensed (68)Ga-DOTATOC (SomaKIT TOC) radiopharmaceutical for the utility of PET imaging in patients with NETs. This preparation can be robustly implemented into routine clinical practice. BMJ Publishing Group 2020-03-17 /pmc/articles/PMC7078687/ /pubmed/32188715 http://dx.doi.org/10.1136/esmoopen-2019-000650 Text en © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, any changes made are indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Manoharan, Prakash
Lamarca, Angela
Navalkissoor, Shaunak
Calero, Jose
Chan, Pei San
Julyan, Peter
Sierra, Maribel
Caplin, Martyn
Valle, Juan
Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
title Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
title_full Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
title_fullStr Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
title_full_unstemmed Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
title_short Safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-DOTA0-Tyr3-octreotide ((68)Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
title_sort safety, tolerability and clinical implementation of ‘ready-to-use’ (68)gallium-dota0-tyr3-octreotide ((68)ga-dotatoc) (somakit toc) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (gep-nets)
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078687/
https://www.ncbi.nlm.nih.gov/pubmed/32188715
http://dx.doi.org/10.1136/esmoopen-2019-000650
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