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ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours

BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are “wild type”). It is unknown whether these antibodies, s...

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Autores principales: Segelov, Eva, Waring, Paul, Desai, Jayesh, Wilson, Kate, Gebski, Val, Thavaneswaran, Subotheni, Elez, Elena, Underhill, Craig, Pavlakis, Nick, Chantrill, Lorraine, Nott, Louise, Jefford, Michael, Khasraw, Mustafa, Day, Fiona, Wasan, Harpreet, Ciardiello, Fortunato, Karapetis, Chris, Joubert, Warren, van Hazel, Guy, Haydon, Andrew, Price, Tim, Tejpar, Sabine, Tebbutt, Niall, Shapiro, Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886432/
https://www.ncbi.nlm.nih.gov/pubmed/27246726
http://dx.doi.org/10.1186/s12885-016-2389-8
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author Segelov, Eva
Waring, Paul
Desai, Jayesh
Wilson, Kate
Gebski, Val
Thavaneswaran, Subotheni
Elez, Elena
Underhill, Craig
Pavlakis, Nick
Chantrill, Lorraine
Nott, Louise
Jefford, Michael
Khasraw, Mustafa
Day, Fiona
Wasan, Harpreet
Ciardiello, Fortunato
Karapetis, Chris
Joubert, Warren
van Hazel, Guy
Haydon, Andrew
Price, Tim
Tejpar, Sabine
Tebbutt, Niall
Shapiro, Jeremy
author_facet Segelov, Eva
Waring, Paul
Desai, Jayesh
Wilson, Kate
Gebski, Val
Thavaneswaran, Subotheni
Elez, Elena
Underhill, Craig
Pavlakis, Nick
Chantrill, Lorraine
Nott, Louise
Jefford, Michael
Khasraw, Mustafa
Day, Fiona
Wasan, Harpreet
Ciardiello, Fortunato
Karapetis, Chris
Joubert, Warren
van Hazel, Guy
Haydon, Andrew
Price, Tim
Tejpar, Sabine
Tebbutt, Niall
Shapiro, Jeremy
author_sort Segelov, Eva
collection PubMed
description BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are “wild type”). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a “quadruple wild type” tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent. METHODS AND DESIGN: ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with “quadruple wild type” or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer. DISCUSSION: This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the “quadruple wild type”, which may ‘superselect’ for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12612000901808, registered 16 August 2012.
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spelling pubmed-48864322016-06-01 ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours Segelov, Eva Waring, Paul Desai, Jayesh Wilson, Kate Gebski, Val Thavaneswaran, Subotheni Elez, Elena Underhill, Craig Pavlakis, Nick Chantrill, Lorraine Nott, Louise Jefford, Michael Khasraw, Mustafa Day, Fiona Wasan, Harpreet Ciardiello, Fortunato Karapetis, Chris Joubert, Warren van Hazel, Guy Haydon, Andrew Price, Tim Tejpar, Sabine Tebbutt, Niall Shapiro, Jeremy BMC Cancer Study Protocol BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are “wild type”). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a “quadruple wild type” tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent. METHODS AND DESIGN: ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with “quadruple wild type” or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer. DISCUSSION: This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the “quadruple wild type”, which may ‘superselect’ for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12612000901808, registered 16 August 2012. BioMed Central 2016-05-31 /pmc/articles/PMC4886432/ /pubmed/27246726 http://dx.doi.org/10.1186/s12885-016-2389-8 Text en © The Author(s). 2016 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
Segelov, Eva
Waring, Paul
Desai, Jayesh
Wilson, Kate
Gebski, Val
Thavaneswaran, Subotheni
Elez, Elena
Underhill, Craig
Pavlakis, Nick
Chantrill, Lorraine
Nott, Louise
Jefford, Michael
Khasraw, Mustafa
Day, Fiona
Wasan, Harpreet
Ciardiello, Fortunato
Karapetis, Chris
Joubert, Warren
van Hazel, Guy
Haydon, Andrew
Price, Tim
Tejpar, Sabine
Tebbutt, Niall
Shapiro, Jeremy
ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
title ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
title_full ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
title_fullStr ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
title_full_unstemmed ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
title_short ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
title_sort icecream: randomised phase ii study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either kras, nras, braf and pi3kca wild type, or g13d mutated tumours
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886432/
https://www.ncbi.nlm.nih.gov/pubmed/27246726
http://dx.doi.org/10.1186/s12885-016-2389-8
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