The University of Southampton
University of Southampton Institutional Repository

CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.

METHODS: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).

DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.

TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.

Journal Article
1745-6215
1-10
Fennell, Dean A.
e85713c5-cf7d-4d9c-b0de-f4302baa08ab
Kirkpatrick, Emma
ef4472be-90bf-400a-b100-e9d26cb907fc
Cozens, Kelly
ad334c90-643c-4e72-a957-7d3d15a938ce
Nye, Mavis
ec13c8e7-5c59-4c4e-982e-5d29fbe52aee
Lester, Jason
3a715211-2b06-4c31-b02b-ceeb9e757a2a
Hanna, Gerard
41388106-e733-4cd7-b7d5-586ed0bd26f3
Steele, Nicola
c695672a-88b8-492e-8fc8-4afa2f6d356d
Szlosarek, Peter
a68a9a12-32ea-40fa-a542-2ea91b6d7699
Danson, Sarah
dc545bf0-6b2f-462d-93c2-9c9636fc3c44
Lord, Joanne
fd3b2bf0-9403-466a-8184-9303bdc80a9a
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Barnes, Daniel
47fc1ecb-756b-4516-b938-67ad5091f06a
Hill, Stephanie
3f617230-e8df-4d39-98eb-a7f4814ebd1f
Kalevras, Michail
4876a5c6-1a5c-4c11-b52f-117de7824b59
Maishman, Thomas
cf4259a4-0eef-4975-9c9d-a2c3d594f989
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Fennell, Dean A.
e85713c5-cf7d-4d9c-b0de-f4302baa08ab
Kirkpatrick, Emma
ef4472be-90bf-400a-b100-e9d26cb907fc
Cozens, Kelly
ad334c90-643c-4e72-a957-7d3d15a938ce
Nye, Mavis
ec13c8e7-5c59-4c4e-982e-5d29fbe52aee
Lester, Jason
3a715211-2b06-4c31-b02b-ceeb9e757a2a
Hanna, Gerard
41388106-e733-4cd7-b7d5-586ed0bd26f3
Steele, Nicola
c695672a-88b8-492e-8fc8-4afa2f6d356d
Szlosarek, Peter
a68a9a12-32ea-40fa-a542-2ea91b6d7699
Danson, Sarah
dc545bf0-6b2f-462d-93c2-9c9636fc3c44
Lord, Joanne
fd3b2bf0-9403-466a-8184-9303bdc80a9a
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Barnes, Daniel
47fc1ecb-756b-4516-b938-67ad5091f06a
Hill, Stephanie
3f617230-e8df-4d39-98eb-a7f4814ebd1f
Kalevras, Michail
4876a5c6-1a5c-4c11-b52f-117de7824b59
Maishman, Thomas
cf4259a4-0eef-4975-9c9d-a2c3d594f989
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d

Fennell, Dean A., Kirkpatrick, Emma, Cozens, Kelly, Nye, Mavis, Lester, Jason, Hanna, Gerard, Steele, Nicola, Szlosarek, Peter, Danson, Sarah, Lord, Joanne, Ottensmeier, Christian, Barnes, Daniel, Hill, Stephanie, Kalevras, Michail, Maishman, Thomas and Griffiths, Gareth (2018) CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial. Trials, 19 (233), 1-10. (doi:10.1186/s13063-018-2602-y).

Record type: Article

Abstract

BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.

METHODS: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).

DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.

TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.

Text
s13063-018-2602-y - Version of Record
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 15 March 2018
e-pub ahead of print date: 18 April 2018
Keywords: Journal Article

Identifiers

Local EPrints ID: 419943
URI: https://eprints.soton.ac.uk/id/eprint/419943
ISSN: 1745-6215
PURE UUID: 04fe44ef-d443-49ec-b32f-1f6e03927552
ORCID for Emma Kirkpatrick: ORCID iD orcid.org/0000-0002-3099-1605
ORCID for Joanne Lord: ORCID iD orcid.org/0000-0003-1086-1624
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

Catalogue record

Date deposited: 24 Apr 2018 16:30
Last modified: 17 Jul 2019 17:22

Export record

Altmetrics

Contributors

Author: Dean A. Fennell
Author: Emma Kirkpatrick ORCID iD
Author: Kelly Cozens
Author: Mavis Nye
Author: Jason Lester
Author: Gerard Hanna
Author: Nicola Steele
Author: Peter Szlosarek
Author: Sarah Danson
Author: Joanne Lord ORCID iD
Author: Daniel Barnes
Author: Stephanie Hill
Author: Michail Kalevras
Author: Thomas Maishman

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×