SNPMiner Trials (Home Page)
Report for Mutation I665V
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There is one clinical trial.
Clinical Trials
1 TrAstuzumab Cardiomyopathy Therapeutic Intervention With Carvedilol (TACTIC) Trial
Breast cancer patients undergoing trastuzumab-based HER2-directed therapy are at risk of heart function decline or heart failure symptoms, but it is unknown if, when, and for how long cardiovascular protective strategies, e.g. with a beta-blocker, could help. This study randomly assigns those taking curative-intent trastuzumab-based HER2-directed therapy to the beta-blocker carvedilol—either when significant heart function decline or subtle early signs of heart injury (either by elevation of a cardiac blood biomarker, i.e. cardiac troponin, or by an abnormal heart ultrasound marker, i.e. global longitudinal strain) are noted, or preventatively before beginning trastuzumab-based HER2-directed therapy. This study will further randomly assign those patients on carvedilol to either discontinuation at the end of trastuzumab-based HER2-directed therapy or continuation for another year, providing much needed clinical trial data on what the best strategy ("tactic") for those at risk of cardiotoxicity with trastuzumab-based HER2-directed therapy is.
NCT03879629 Breast Cancer Drug: Carvedilol MeSH:Cardiomyopathies
HPO:Cardiomyopathy
Correlation of absolute delta change in GLS and LVEF while on trastuzumab and after stopping trastuzumab with the frequency of the following SNPs: trastuzumab-related: p<1x10-5 hits from Norton GWAS (six loci) 130 HER 2 Ile665Val, HER2 Pro1170Ala125, 126, 130, anthracycline-related: ABCB1 rs1128503, ABCB4 rs1149222, ABCC1 rs45511401, ABCC2 res17222723, CAT rs10836235, CBR3 rs1056892, CYBA rs4673, CYP3A4*22 rs35599367, NCF4 rs1883112, RAC2 rs13058338, RARG rs2229774, SLC28A3 rs7853758, TOP2B rs10865801, and UGT 1A6*4 rs1786378374, 150-152, beta-blocker-related: β2-AR Gln27Gln, β1-AR Arg389Arg 80-82 and CYP2D6 polymorphisms (CYP2D6 alleles (*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *19, *20, *29, *35, *36, *40 and *41), as well as 7 CYP2D6 gene duplications (*1 9 N, *2 9 N, *4 9 N, *10 9 N, *17 9 N, *35 9 N and *41 9 N) by use of the AmpliChip CYP450 GeneChip. --- Ile665Val ---
Primary Outcomes
Description: Incidence of heart failure or asymptomatic decline in left-ventricular ejection fraction (LVEF) by >10% in patients whose LVEF is ≥50% or LVEF drop ≥5% in those with a decrease to <50% (primary outcome measure)
Measure: Rate of asymptomatic and symptomatic cardiac dysfunction Time: 1 yearDescription: Reversible LVEF decline to within 5% of baseline (secondary primary outcome measure)
Measure: Rate of reversible cardiac function decline Time: 1 yearSecondary Outcomes
Description: Delta change in LVEF from completion to one year after completion of trastuzumab-based HER2-directed therapy
Measure: Cardiac function changes after completion of HER2-directed therapy Time: 1 yearDescription: Correlation of absolute delta change in GLS and LVEF while on trastuzumab and after stopping trastuzumab with the frequency of the following SNPs: trastuzumab-related: p<1x10-5 hits from Norton GWAS (six loci) 130 HER 2 Ile665Val, HER2 Pro1170Ala125, 126, 130, anthracycline-related: ABCB1 rs1128503, ABCB4 rs1149222, ABCC1 rs45511401, ABCC2 res17222723, CAT rs10836235, CBR3 rs1056892, CYBA rs4673, CYP3A4*22 rs35599367, NCF4 rs1883112, RAC2 rs13058338, RARG rs2229774, SLC28A3 rs7853758, TOP2B rs10865801, and UGT 1A6*4 rs1786378374, 150-152, beta-blocker-related: β2-AR Gln27Gln, β1-AR Arg389Arg 80-82 and CYP2D6 polymorphisms (CYP2D6 alleles (*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *19, *20, *29, *35, *36, *40 and *41), as well as 7 CYP2D6 gene duplications (*1 9 N, *2 9 N, *4 9 N, *10 9 N, *17 9 N, *35 9 N and *41 9 N) by use of the AmpliChip CYP450 GeneChip
Measure: Gene variants and risk of cardiotoxicity and response to therapy Time: 2 years