title: The ASAMET trial: a randomized, phase II, double-blind, placebo-controlled, multicenter, 2 × 2 factorial biomarker study of tertiary prevention with low-dose aspirin and metformin in stage I-III colorectal cancer patients
creator: Petrera, Marilena
creator: Paleari, Laura
creator: Clavarezza, Matteo
creator: Puntoni, Matteo
creator: Caviglia, Silvia
creator: Briata, Irene Maria
creator: Oppezzi, Massimo
creator: Mihajlovic Mislej, Eva
creator: Stabuc, Borut
creator: Gnant, Michael
creator: Bachleitner-Hofmann, Thomas
creator: Roth, Wilfried
creator: Scherer, Dominique
creator: Haefeli, Walter-E.
creator: Ulrich, Cornelia M.
creator: DeCensi, Andrea
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Background: Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin can reduce colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin has also been associated with decreased colon adenoma recurrence in clinical trials and lower CRC incidence and mortality in epidemiological studies in diabetics. While both drugs have been tested as single agents, their combination has not been tested in cancer prevention trials.       Methods/design: This is a randomized, placebo-controlled, double-blind, 2 × 2 biomarker trial of aspirin and metformin to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery, 160 patients with stage I-III CRC are randomly assigned in a four-arm trial to either aspirin (100 mg day), metformin (850 mg bis in die), their combination, or placebo for one year. The primary endpoint biomarker is the change of IHC expression of nuclear factor kappa-B (NFκB) in the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in two paired colonoscopies one year apart. Additional biomarkers will include: 1) the measurement of circulating IL-6, CRP and VEGF; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of genetic markers with treatment response as assessed by next generation sequencing of primary tumors; 4) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome wide gene expression arrays; and 5) the evaluation of adenoma occurrence at 1 year.    Discussion: A favorable biomarker modulation by aspirin and metformin may provide important clues for a subsequent phase III adjuvant trial aimed at preventing second primary cancer, delaying recurrence and improving prognosis in patients with CRC.    Trial registration: EudraCT Number: 2015–004824-77; ClinicalTrial.gov    Identifier: NCT03047837.   Registered on February 1, 2017.
publisher: BioMed Central ; Springer
date: 2018
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/25724/1/12885_2018_Article_5126.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-257244
identifier:   Petrera, Marilena ; Paleari, Laura ; Clavarezza, Matteo ; Puntoni, Matteo ; Caviglia, Silvia ; Briata, Irene Maria ; Oppezzi, Massimo ; Mihajlovic Mislej, Eva ; Stabuc, Borut ; Gnant, Michael ; Bachleitner-Hofmann, Thomas ; Roth, Wilfried ; Scherer, Dominique ; Haefeli, Walter-E. ; Ulrich, Cornelia M. ; DeCensi, Andrea  (2018) The ASAMET trial: a randomized, phase II, double-blind, placebo-controlled, multicenter, 2 × 2 factorial biomarker study of tertiary prevention with low-dose aspirin and metformin in stage I-III colorectal cancer patients.  BMC Cancer, 18 (1210).  pp. 1-9.  ISSN 1471-2407     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/25724/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng