SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03879629

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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
MeSH: Cardiomyopathies
HPO: Cardiomyopathy

1 Interventions

Name: Carvedilol

Description: oral Carvedilol maximally tolerated doses 3.125 mg to 25 mg twice a day

Type: Drug

Pre-Emptive Strategy Reactive Strategy Standard of Care


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 year

Description: Reversible LVEF decline to within 5% of baseline (secondary primary outcome measure)

Measure: Rate of reversible cardiac function decline

Time: 1 year

Secondary 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 year

Description: 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

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 I665V

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 ---



HPO Nodes


HPO:
Cardiomyopathy
Genes 431
TPM1 TPM2 TPM3 CDKN1C TACO1 HFE H19-ICR SDHAF1 TREX1 ERBB3 ERCC2 EYA4 ERCC3 BRIP1 ERCC4 ACADL HLA-B ACADS PDGFRA ACADVL MICOS13 PDHA1 DNAJC19 ENPP1 SPEG SMC1A ACTA1 MC2R PEX1 ACTC1 PEX6 PEX7 DPM3 PEX10 PEX12 PEX13 PEX14 ANO5 HMGCL KLHL41 ACTN2 CHKB ADAR TTN HNRNPA1 TTPA TTR TRIP4 HNRNPA2B1 ADCY5 WARS2 ELAC2 PGM1 RYR1 RYR2 RNU4ATAC FANCA FANCC FANCD2 FANCE SLC25A3 SLC2A10 FAH FANCB FANCF FANCG PHYH AARS2 FKTN CLN3 AGL RAB3GAP2 RNASEH2C HPS1 SCN5A MIPEP MIB1 COA5 AHCY GPC4 PEX16 HRAS SCO1 GTF2H5 PKP2 MMP1 MAD2L2 MTO1 FTO PRKAG2 FHL1 FHL2 POMK GMPPB PLN LTBP4 SLC30A10 D2HGDH SDHA SDHB VCL VCP SDHD PMM2 HJV POMT2 TMEM126A NDUFB11 COL7A1 FLNC FOXRED1 MYOT NDUFAF5 ANK1 NEBL TAPT1 SLC25A4 CLIP2 CISD2 RNASEH2A FKRP SGCA WFS1 SGCB SGCD ACAD9 SGSH FOS RRM2B POLG GNPTAB PEX3 NDUFAF3 BAG3 AGPAT2 COX6B1 DOLK SLC19A2 KCNAB2 COX7B COX8A COX10 POMGNT1 COX15 TWNK XK SAMHD1 FASTKD2 TMEM43 GATA5 POMT1 IDH2 TXNRD2 FXN PPARG XRCC2 CPT1A XRCC4 CPT2 FANCM GTF2IRD1 IDUA SKI TCAP SLC40A1 COA8 ABCC6 RBM20 PEX26 RBCK1 NDUFA11 SLC4A1 EPG5 PPP1CB MTFMT LIMS2 CRYAB NBAS LIPT1 VAC14 PIGT NDUFAF4 IGF2 ACAD8 ARSB ATP6 COX1 COX2 UBE2T COX3 KLF1 NEK8 FLAD1 ANKRD1 ND1 ND2 SLC22A5 ND3 ND4 NAXD MRPS14 PPA2 ND5 ND6 ANKRD11 MPLKIP GATAD1 AGK KBTBD13 TRNE TRNF NDUFAF6 CAVIN1 TRNH TRNK TRNL1 HAMP RERE TRNN TRNQ TRNS1 TRNS2 RNASEH1 TRNT TRNV TRNW SUFU MAP2K1 MAP2K2 PRDM16 NEXN SLX4 MMUT H19 MGME1 ATPAF2 SOS1 MYBPC3 ATP5F1D ATP5F1E GABRD COX20 UBR1 IL12B ATP6V1A MYH6 MYH7 ANKS6 NDUFS7 MYL2 MYL3 DCAF8 PSEN1 PSEN2 PET100 SPTA1 SPTB TMEM126B MRPL44 RNF113A VPS33A NAGA NAGLU MAP3K20 GATA4 MYOZ2 BBS2 GBE1 CDH23 NDUFA2 NDUFA4 PEX11B GPR101 ITGA7 NEB NDUFA9 NDUFA10 COQ2 BCS1L NDUFB8 NDUFS1 NDUFS2 MRPS22 NDUFS3 STAR NDUFV1 NDUFS4 ITPA NDUFS8 NDUFV2 FBXL4 IFIH1 DES GJA5 JUP COA6 PTPN11 NEU1 NF1 GLA GPC3 NDUFA12 BRCA1 GLB1 ALMS1 BRAF BRCA2 CLPB FIG4 KCNH1 SURF1 KCNJ8 MYPN TMEM70 SYNE2 VPS13A PEX19 C1QBP PEX2 PEX5 KCNQ1 DLD DMD SARDH MYO18B RMND1 GTPBP3 KCNQ1OT1 GNS ALG1 TAZ RAD51 RAD51C RNASEH2B KRAS RAF1 LIAS SCO2 NPPA PNPLA2 SLC25A20 NRAS DSC2 MLX NUP107 GNE DSG2 NDUFAF2 DSP COG7 DTNA SYNE1 TAF1A HGSNAT SLC19A3 LAMA2 LAMA3 LAMA4 JPH2 BAZ1B LAMB3 ABCC9 LAMC2 LAMP2 FANCL AIP CAV1 RFC2 ECHS1 PPCS SHOC2 SELENON BOLA3 OPA1 CSRP3 PALB2 TSFM GSN RFWD3 MLYCD YARS2 TFR2 RIT1 TGFB1 TGFB3 NDUFA13 RMRP USP8 TNNI3K LIMK1 GTF2E2 LDB3 TRNT1 GTF2I ABHD5 NDUFAF1 LMNA ATAD3A TK2 COQ4 GUSB FANCI GYG1 GYS1 MRAP TMPO BSCL2 HSD17B10 ELN HADHA MRPL3 HADHB HADH EMD TANGO2 TNNC1 POLG2 TNNI3 KAT6B HBB TNNT2 PCCA PCCB NNT HCCS HACD1 TBL2 TOP3A EPB42 COX14 TPI1