TY  - JOUR
PB  - BioMed Central ; Springer
TI  - 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
N2  - 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 (NF?B) 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.
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/25724/
ID  - heidok25724
JF  - BMC Cancer
IS  - 1210
EP  - 9
VL  - 18
AV  - public
Y1  - 2018///
CY  - London ; Berlin, Heidelberg
SN  - 1471-2407
A1  - Petrera, Marilena
A1  - Paleari, Laura
A1  - Clavarezza, Matteo
A1  - Puntoni, Matteo
A1  - Caviglia, Silvia
A1  - Briata, Irene Maria
A1  - Oppezzi, Massimo
A1  - Mihajlovic Mislej, Eva
A1  - Stabuc, Borut
A1  - Gnant, Michael
A1  - Bachleitner-Hofmann, Thomas
A1  - Roth, Wilfried
A1  - Scherer, Dominique
A1  - Haefeli, Walter-E.
A1  - Ulrich, Cornelia M.
A1  - DeCensi, Andrea
SP  - 1
KW  - Colorectal cancer
KW  -  Aspirin
KW  -  Metformin
KW  -  Biomarkers
KW  -  Chemoprevention
KW  -  Tertiary prevention
ER  -