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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

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 and Shapiro, Jeremy 2016, 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, BMC cancer, vol. 16, pp. 1-8, doi: 10.1186/s12885-016-2389-8.

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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
Author(s) 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, MustafaORCID iD for Khasraw, Mustafa orcid.org/0000-0003-3249-9849
Day, Fiona
Wasan, Harpreet
Ciardiello, Fortunato
Karapetis, Chris
Joubert, Warren
van Hazel, Guy
Haydon, Andrew
Price, Tim
Tejpar, Sabine
Tebbutt, Niall
Shapiro, Jeremy
Journal name BMC cancer
Volume number 16
Article ID 339
Start page 1
End page 8
Total pages 8
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2016
ISSN 1471-2407
Keyword(s) cetuximab
clinical trial
colorectal tumours
irinotecan
tumour mutations
science and technology
life sciences and biomedicine
oncology
Summary 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.
Language eng
DOI 10.1186/s12885-016-2389-8
Field of Research 1112 Oncology And Carcinogenesis
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30103399

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.