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NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC)

NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC)
NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC)

Introduction: poorly differentiated (PD), extrapulmonary (EP), neuroendocrine carcinomas (NECs) are rare but aggressive neuroendocrine neoplasms. First-line treatment for advanced disease is an etoposide and platinum-based chemotherapy combination. There is no established second-line treatment for patients with PD-EP-NEC, and this is an area of unmet need.

Methods and analysis: NET-02 is a UK, multicentre, randomised (1:1), parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive PD-EP-NEC. One hundred and two eligible participants will be randomised to receive either nal-IRI/5-FU/folinic acid or docetaxel. The primary objective is to determine the 6-month progression-free survival (PFS) rate. The secondary objectives of this study are to determine PFS, overall survival, objective response rate, toxicity, quality of life and whether neuron-specific enolase is predictive of treatment response. If either treatment is found to have a 6-month PFS rate of at least 25%, that treatment will be considered for a phase III trial. If both treatments meet this target, prespecified selection criteria will be applied to establish which treatment to take forward.

Ethics and dissemination: this study has ethical approval from the Greater Manchester Central Research Ethics Committee (reference no. 18/NW/0031) and clinical trial authorisation from the Medicine and Healthcare Products Regulatory Agency. Results will be published in peer-reviewed journals and uploaded to the European Union Clinical Trials Register.

Trial registration numbers: ISRCTN10996604, NCT03837977, EudraCT Number: 2017-002453-11.

antineoplastic combined chemotherapy protocols/therapeutic use, carcinoma, neuroendocrine/drug therapy, clinical trials, phase II as topic, docetaxel/therapeutic use, fluorouracil/therapeutic use, humans, irinotecan/therapeutic use, leucovorin/therapeutic use, multicenter studies as topic, quality of life, randomized controlled trials as topic
2044-6055
e034527
Craig, Zoe
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Swain, Jayne
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Batman, Emma
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Wadsley, Jonathan
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Reed, Nicholas
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Faluyi, Olusola
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Cave, Judith
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Sharma, Rohini
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Chau, Ian
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Wall, Lucy
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Lamarca, Angela
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Hubner, R
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Mansoor, Wasat
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Sarker, Debashis
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Meyer, Tim
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Cairns, David A
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Howard, Helen
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Valle, Juan W
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McNamara, Mairéad G
c3b9d2cc-ebef-47f7-a027-b8014f763f5e
Craig, Zoe
0be547b7-c1dc-4f32-bd10-645df0182399
Swain, Jayne
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Batman, Emma
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Wadsley, Jonathan
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Reed, Nicholas
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Faluyi, Olusola
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Cave, Judith
60c67e39-121a-49ca-8594-93e8e456464f
Sharma, Rohini
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Chau, Ian
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Wall, Lucy
ca544bbc-6662-4df6-9a5c-7abb088ab64f
Lamarca, Angela
283eb480-1dd5-4341-89ad-c36273322a6f
Hubner, R
23340894-eabf-4cb5-a41e-ae4d23a2419e
Mansoor, Wasat
61e3b9be-8645-4e86-ba70-2dacf7af563e
Sarker, Debashis
1b3b1b23-092b-4f05-8fe5-7f9922e2d3e7
Meyer, Tim
28c8fc8e-873f-4278-9443-cb7c9f9f487f
Cairns, David A
8177d1d3-73de-44b2-a2f5-292eededa50d
Howard, Helen
6dbdb565-9d44-438c-a042-584116877cf8
Valle, Juan W
2a6166b1-933c-4e35-8d12-0ccad8318c56
McNamara, Mairéad G
c3b9d2cc-ebef-47f7-a027-b8014f763f5e

Craig, Zoe, Swain, Jayne, Batman, Emma, Wadsley, Jonathan, Reed, Nicholas, Faluyi, Olusola, Cave, Judith, Sharma, Rohini, Chau, Ian, Wall, Lucy, Lamarca, Angela, Hubner, R, Mansoor, Wasat, Sarker, Debashis, Meyer, Tim, Cairns, David A, Howard, Helen, Valle, Juan W and McNamara, Mairéad G (2020) NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC). BMJ Open, 10 (2), e034527. (doi:10.1136/bmjopen-2019-034527).

Record type: Article

Abstract

Introduction: poorly differentiated (PD), extrapulmonary (EP), neuroendocrine carcinomas (NECs) are rare but aggressive neuroendocrine neoplasms. First-line treatment for advanced disease is an etoposide and platinum-based chemotherapy combination. There is no established second-line treatment for patients with PD-EP-NEC, and this is an area of unmet need.

Methods and analysis: NET-02 is a UK, multicentre, randomised (1:1), parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive PD-EP-NEC. One hundred and two eligible participants will be randomised to receive either nal-IRI/5-FU/folinic acid or docetaxel. The primary objective is to determine the 6-month progression-free survival (PFS) rate. The secondary objectives of this study are to determine PFS, overall survival, objective response rate, toxicity, quality of life and whether neuron-specific enolase is predictive of treatment response. If either treatment is found to have a 6-month PFS rate of at least 25%, that treatment will be considered for a phase III trial. If both treatments meet this target, prespecified selection criteria will be applied to establish which treatment to take forward.

Ethics and dissemination: this study has ethical approval from the Greater Manchester Central Research Ethics Committee (reference no. 18/NW/0031) and clinical trial authorisation from the Medicine and Healthcare Products Regulatory Agency. Results will be published in peer-reviewed journals and uploaded to the European Union Clinical Trials Register.

Trial registration numbers: ISRCTN10996604, NCT03837977, EudraCT Number: 2017-002453-11.

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More information

Accepted/In Press date: 20 January 2020
e-pub ahead of print date: 5 February 2020
Keywords: antineoplastic combined chemotherapy protocols/therapeutic use, carcinoma, neuroendocrine/drug therapy, clinical trials, phase II as topic, docetaxel/therapeutic use, fluorouracil/therapeutic use, humans, irinotecan/therapeutic use, leucovorin/therapeutic use, multicenter studies as topic, quality of life, randomized controlled trials as topic

Identifiers

Local EPrints ID: 478146
URI: http://eprints.soton.ac.uk/id/eprint/478146
ISSN: 2044-6055
PURE UUID: eecfa11d-e069-4f28-b29d-5f5f07f30df6

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Date deposited: 22 Jun 2023 16:44
Last modified: 17 Mar 2024 02:04

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Contributors

Author: Zoe Craig
Author: Jayne Swain
Author: Emma Batman
Author: Jonathan Wadsley
Author: Nicholas Reed
Author: Olusola Faluyi
Author: Judith Cave
Author: Rohini Sharma
Author: Ian Chau
Author: Lucy Wall
Author: Angela Lamarca
Author: R Hubner
Author: Wasat Mansoor
Author: Debashis Sarker
Author: Tim Meyer
Author: David A Cairns
Author: Helen Howard
Author: Juan W Valle
Author: Mairéad G McNamara

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