ELEVATE - evaluating Temozolomide and Nivolumab in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma with MGMT methylation: study protocol for a single arm phase II trial.
Adenocarcinoma
/ chemically induced
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Clinical Trials, Phase II as Topic
DNA Modification Methylases
/ genetics
DNA Repair Enzymes
/ genetics
Humans
Methylation
Neoplasm Recurrence, Local
/ drug therapy
Nivolumab
Quality of Life
Temozolomide
/ therapeutic use
Tumor Suppressor Proteins
Immunotherapy
MGMT methylated
Oesophagogastric adenocarcinoma
Phase II
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
01 Sep 2022
01 Sep 2022
Historique:
received:
15
02
2022
accepted:
13
07
2022
entrez:
1
9
2022
pubmed:
2
9
2022
medline:
8
9
2022
Statut:
epublish
Résumé
For patients with oesophagogastric adenocarcinoma, surgery is the only curative option and despite the use of multimodality therapy, which combines it with chemotherapy and/or radiotherapy, more than 50% of patients will relapse and die. Many UK patients present with advanced disease which is already inoperable or metastatic at diagnosis. For these patients, standard care chemotherapy only offers them survival of less than a year. Nivolumab, a checkpoint blockade inhibitor, has been found to work in some advanced cancers. It is proposed, for those where immunotherapy hasn't worked, that these immunologically evasive tumours need to be sensitized to immunotherapy drugs to allow them to act. ELEVATE is a single arm phase II trial testing the overall response to nivolumab following temozolomide treatment in patients with advanced unresectable previously treated adenocarcinoma which is O ELEVATE will provide evidence for whether giving nivolumab after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma is safe and biologically effective prior to future randomised trials. EudraCT Number: 2020-004771-41 (issued 01 October 2020); ISCRTN11398887 (registered 14 July 2021).
Sections du résumé
BACKGROUND
BACKGROUND
For patients with oesophagogastric adenocarcinoma, surgery is the only curative option and despite the use of multimodality therapy, which combines it with chemotherapy and/or radiotherapy, more than 50% of patients will relapse and die. Many UK patients present with advanced disease which is already inoperable or metastatic at diagnosis. For these patients, standard care chemotherapy only offers them survival of less than a year. Nivolumab, a checkpoint blockade inhibitor, has been found to work in some advanced cancers. It is proposed, for those where immunotherapy hasn't worked, that these immunologically evasive tumours need to be sensitized to immunotherapy drugs to allow them to act.
METHODS
METHODS
ELEVATE is a single arm phase II trial testing the overall response to nivolumab following temozolomide treatment in patients with advanced unresectable previously treated adenocarcinoma which is O
DISCUSSION
CONCLUSIONS
ELEVATE will provide evidence for whether giving nivolumab after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma is safe and biologically effective prior to future randomised trials.
TRIAL REGISTRATIONS
BACKGROUND
EudraCT Number: 2020-004771-41 (issued 01 October 2020); ISCRTN11398887 (registered 14 July 2021).
Identifiants
pubmed: 36050653
doi: 10.1186/s12885-022-09891-9
pii: 10.1186/s12885-022-09891-9
pmc: PMC9434527
doi:
Substances chimiques
Tumor Suppressor Proteins
0
Nivolumab
31YO63LBSN
DNA Modification Methylases
EC 2.1.1.-
MGMT protein, human
EC 2.1.1.63
DNA Repair Enzymes
EC 6.5.1.-
Temozolomide
YF1K15M17Y
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
946Subventions
Organisme : Cancer Research UK
ID : 23924
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 25352
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Lancet. 2010 Aug 28;376(9742):687-97
pubmed: 20728210
N Engl J Med. 2015 Nov 5;373(19):1803-13
pubmed: 26406148
Lancet. 2016 May 7;387(10031):1909-20
pubmed: 26952546
Lancet. 2014 Jan 4;383(9911):31-39
pubmed: 24094768
Cancer Immunol Immunother. 2009 Oct;58(10):1627-34
pubmed: 19221744
J Clin Oncol. 2018 Oct 1;36(28):2836-2844
pubmed: 30110194
Neuro Oncol. 2011 Apr;13(4):393-400
pubmed: 21339188
Neuro Oncol. 2019 Jun 10;21(6):730-741
pubmed: 30668768
N Engl J Med. 2008 Jan 3;358(1):36-46
pubmed: 18172173
Mol Cancer Ther. 2013 May;12(5):809-18
pubmed: 23443801
Lancet. 2002 May 18;359(9319):1727-33
pubmed: 12049861
N Engl J Med. 2012 May 31;366(22):2074-84
pubmed: 22646630
Nature. 2017 Dec 7;552(7683):116-120
pubmed: 29186113
Stat Med. 2001 Mar 30;20(6):859-66
pubmed: 11252008
Nat Med. 2018 Sep;24(9):1449-1458
pubmed: 30013197
PLoS One. 2016 Feb 01;11(2):e0148139
pubmed: 26829221
J Clin Oncol. 2012 May 1;30(13):1513-8
pubmed: 22412140
Lancet Oncol. 2014 Jan;15(1):78-86
pubmed: 24332238
Lancet Oncol. 2020 Oct;21(10):1309-1316
pubmed: 32853557
Lancet Oncol. 2014 Oct;15(11):1224-35
pubmed: 25240821
N Engl J Med. 2015 Jul 2;373(1):23-34
pubmed: 26027431
Ann Intern Med. 2013 Feb 5;158(3):200-7
pubmed: 23295957
Gut. 2013 Oct;62(10):1406-14
pubmed: 22917659
Ann Oncol. 2014 Feb;25(2):404-8
pubmed: 24379162
N Engl J Med. 2006 Jul 6;355(1):11-20
pubmed: 16822992
Neuro Oncol. 2011 Mar;13(3):324-33
pubmed: 21149254
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
N Engl J Med. 2015 Jul 9;373(2):123-35
pubmed: 26028407
N Engl J Med. 2015 Jun 25;372(26):2521-32
pubmed: 25891173
Oncoimmunology. 2014 Jan 1;3(1):e27357
pubmed: 24790790
Clin Cancer Res. 2011 Aug 15;17(16):5473-80
pubmed: 21737504
JAMA Oncol. 2018 May 10;4(5):e180013
pubmed: 29543932
J Clin Oncol. 2006 Nov 1;24(31):4991-7
pubmed: 17075117
Lancet. 2018 Jul 14;392(10142):123-133
pubmed: 29880231