eprintid: 25724 rev_number: 14 eprint_status: archive userid: 1589 dir: disk0/00/02/57/24 datestamp: 2019-01-30 14:55:12 lastmod: 2024-04-10 09:06:26 status_changed: 2019-01-30 14:55:12 type: article metadata_visibility: show creators_name: Petrera, Marilena creators_name: Paleari, Laura creators_name: Clavarezza, Matteo creators_name: Puntoni, Matteo creators_name: Caviglia, Silvia creators_name: Briata, Irene Maria creators_name: Oppezzi, Massimo creators_name: Mihajlovic Mislej, Eva creators_name: Stabuc, Borut creators_name: Gnant, Michael creators_name: Bachleitner-Hofmann, Thomas creators_name: Roth, Wilfried creators_name: Scherer, Dominique creators_name: Haefeli, Walter-E. creators_name: Ulrich, Cornelia M. creators_name: DeCensi, Andrea 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 subjects: ddc-610 divisions: i-54600 divisions: i-911800 keywords: Colorectal cancer, Aspirin, Metformin, Biomarkers, Chemoprevention, Tertiary prevention abstract: 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. date: 2018 publisher: BioMed Central ; Springer id_scheme: DOI ppn_swb: 1655083163 own_urn: urn:nbn:de:bsz:16-heidok-257244 language: eng bibsort: PETRERAMARTHEASAMETT2018 full_text_status: public publication: BMC Cancer volume: 18 number: 1210 place_of_pub: London ; Berlin, Heidelberg pagerange: 1-9 issn: 1471-2407 citation: 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 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/25724/1/12885_2018_Article_5126.pdf