Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)

BACKGROUND: Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objec...

Descripción completa

Detalles Bibliográficos
Autores principales: Braat, Arthur J. A. T., Kwekkeboom, Dik J., Kam, Boen L. R., Teunissen, Jaap J. M., de Herder, Wouter W., Dreijerink, Koen M. A., van Rooij, Rob, Krijger, Gerard C., de Jong, Hugo W. A. M., van den Bosch, Maurice A. A. J., Lam, Marnix G. E. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Study Protocol
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003090/
https://www.ncbi.nlm.nih.gov/pubmed/29902988
http://dx.doi.org/10.1186/s12876-018-0817-8
_version_ 1783332303381987328
author Braat, Arthur J. A. T.
Kwekkeboom, Dik J.
Kam, Boen L. R.
Teunissen, Jaap J. M.
de Herder, Wouter W.
Dreijerink, Koen M. A.
van Rooij, Rob
Krijger, Gerard C.
de Jong, Hugo W. A. M.
van den Bosch, Maurice A. A. J.
Lam, Marnix G. E. H.
author_facet Braat, Arthur J. A. T.
Kwekkeboom, Dik J.
Kam, Boen L. R.
Teunissen, Jaap J. M.
de Herder, Wouter W.
Dreijerink, Koen M. A.
van Rooij, Rob
Krijger, Gerard C.
de Jong, Hugo W. A. M.
van den Bosch, Maurice A. A. J.
Lam, Marnix G. E. H.
author_sort Braat, Arthur J. A. T.
collection PubMed
description BACKGROUND: Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization ((166)Ho-RE) after PRRT with lutetium-177 ((177)Lu)-DOTATATE. METHODS: The HEPAR PLUS trial (“Holmium Embolization Particles for Arterial Radiotherapy Plus (177)Lu-DOTATATE in Salvage NET patients”) is a single centre, interventional, non-randomized, non-comparative, open label study. In this phase 2 study 30–48 patients with > 3 measurable liver metastases according to RECIST 1.1 will receive additional (166)Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq (177)Lu-DOTATATE. Primary objectives are to assess tumour response, complete and partial response according to RECIST 1.1, and toxicity, based on CTCAE v4.03, 3 months after (166)Ho-RE. Secondary endpoints include biochemical response, quality of life, biodistribution and dosimetry. DISCUSSION: This is the first prospective study to combine PRRT with (177)Lu-DOTATATE and additional (166)Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using (166)Ho-RE may lead to an improved response rate without significant additional side-effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02067988, 13 February 2014. Protocol version: 6, 30 november 2016.
format Online
Article
Text
id pubmed-6003090
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-60030902018-07-06 Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial) Braat, Arthur J. A. T. Kwekkeboom, Dik J. Kam, Boen L. R. Teunissen, Jaap J. M. de Herder, Wouter W. Dreijerink, Koen M. A. van Rooij, Rob Krijger, Gerard C. de Jong, Hugo W. A. M. van den Bosch, Maurice A. A. J. Lam, Marnix G. E. H. BMC Gastroenterol Study Protocol BACKGROUND: Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization ((166)Ho-RE) after PRRT with lutetium-177 ((177)Lu)-DOTATATE. METHODS: The HEPAR PLUS trial (“Holmium Embolization Particles for Arterial Radiotherapy Plus (177)Lu-DOTATATE in Salvage NET patients”) is a single centre, interventional, non-randomized, non-comparative, open label study. In this phase 2 study 30–48 patients with > 3 measurable liver metastases according to RECIST 1.1 will receive additional (166)Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq (177)Lu-DOTATATE. Primary objectives are to assess tumour response, complete and partial response according to RECIST 1.1, and toxicity, based on CTCAE v4.03, 3 months after (166)Ho-RE. Secondary endpoints include biochemical response, quality of life, biodistribution and dosimetry. DISCUSSION: This is the first prospective study to combine PRRT with (177)Lu-DOTATATE and additional (166)Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using (166)Ho-RE may lead to an improved response rate without significant additional side-effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02067988, 13 February 2014. Protocol version: 6, 30 november 2016. BioMed Central 2018-06-15 /pmc/articles/PMC6003090/ /pubmed/29902988 http://dx.doi.org/10.1186/s12876-018-0817-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Braat, Arthur J. A. T.
Kwekkeboom, Dik J.
Kam, Boen L. R.
Teunissen, Jaap J. M.
de Herder, Wouter W.
Dreijerink, Koen M. A.
van Rooij, Rob
Krijger, Gerard C.
de Jong, Hugo W. A. M.
van den Bosch, Maurice A. A. J.
Lam, Marnix G. E. H.
Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)
title Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)
title_full Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)
title_fullStr Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)
title_full_unstemmed Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)
title_short Additional hepatic (166)Ho-radioembolization in patients with neuroendocrine tumours treated with (177)Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial)
title_sort additional hepatic (166)ho-radioembolization in patients with neuroendocrine tumours treated with (177)lu-dotatate; a single center, interventional, non-randomized, non-comparative, open label, phase ii study (hepar plus trial)
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003090/
https://www.ncbi.nlm.nih.gov/pubmed/29902988
http://dx.doi.org/10.1186/s12876-018-0817-8
work_keys_str_mv AT braatarthurjat additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT kwekkeboomdikj additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT kamboenlr additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT teunissenjaapjm additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT deherderwouterw additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT dreijerinkkoenma additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT vanrooijrob additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT krijgergerardc additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT dejonghugowam additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT vandenboschmauriceaaj additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial
AT lammarnixgeh additionalhepatic166horadioembolizationinpatientswithneuroendocrinetumourstreatedwith177ludotatateasinglecenterinterventionalnonrandomizednoncomparativeopenlabelphaseiistudyheparplustrial

Ejemplares similares