SNPMiner Trials: Mutation Report
Report for Mutation F31I
Developed by Shray Alag, 2019.
SNP Clinical Trial Gene
There are 2 clinical trials
Clinical Trials
RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed
for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to
see how well it works in treating young patients with relapsed or refractory solid tumors
NCT02444884 Unspecified Childhood Solid Tumor, Excluding CNS Neuroblastoma Drug: MLN8237
To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and
Val57Ile) thought to potentially influence tumorigenesis. --- Phe31Ile ---
Primary Outcomes
Measure: Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
Time: Up to 21 days (1st cycle) of protocol therapy
Measure: Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
Time: Up to 21 days (1st cycle) of protocol therapy
Description: DLT will be defined as possibly, probably or definitely attributable to MLN8237. The DLT observation period for the purposes of dose-escalation will be the first cycle of therapy
Measure: Adverse events as assessed by (CTCAE) version 4.0
Time: Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]
Description: single-dose AUC, trough estimation, t½ of accumulation
Measure: PK Profile: MLN8237 concentrations in plasma samples
Time: 30 min after the first dose, and at 1,2, 3, 4, 6-8, 24 hours, Day 4 and 7 in Cycle 1
This phase II trial is studying the side effects of and how well alisertib works in treating
young patients with relapsed or refractory solid tumors or leukemia. Alisertib may stop the
growth of cancer cells by blocking some of the enzymes needed for cell growth.
To explore the relationship between polymorphic variations in the
UDP-glucuronosyltransferase gene UGT1A1 and exposure to MLN8237, and to assess 2 common
polymorphic variants in the aurora A kinase gene, Phe31Ile and Val57Ile. --- Phe31Ile ---
Primary Outcomes
Description: For patients with recurrent solid tumors a patient who experienced a complete or partial response according to RECIST version 1.1 criteria is considered a responder. For patients with recurrent acute lymphoblastic leukemia a patient who experiences a bone marrow evaluation with < 5% blast cells on morphological evaluation of bone marrow will be considered a responder. For patients with recurrent acute myelogenous leukemia a patient who experiences a complete remission or complete remission with partial recovery of platelet count according to the AML International Working Group Criteria will be considered a responder.
Measure: Number of Participants With Overall Response
Time: From first dose of alisertib through 6 cycles of protocol therapy or until removal from protocol therapy whichever occurred first.
Secondary Outcomes
Description: The number of patient-cycles in which the adverse event considered grade 3 or higher AE according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 considered by the treating physician to be possibly, probably or definitely related to alisertib.
Measure: Number of Patients Cycles With Grade 3 or Higher Adverse Event
Time: Up to 24 months
Description: Serum concentration of alisertib prior to the first day of administration in nanograms/milliliter.
Measure: Serum Concentration of Alisertib Prior to the First Day of Administration
Time: day 1 of protocol therapy
Description: Serum concentration of alisertib on the first day of administration one hour after administration in nanograms/milliliter.
Measure: Serum Concentration of Alisertib on the First Day of Administration One Hour After Administration
Time: day 1 of protocol therapy
Description: Serum concentration of alisertib on the first day of administration three hours after administration in nanograms/milliliter.
Measure: Serum Concentration of Alisertib on the First Day of Administration Three Hours After Administration
Time: day 1 of protocol therapy
Description: Serum concentration of alisertib on the first day of administration six hours after administration in nanograms/milliliter.
Measure: Serum Concentration of Alisertib on the First Day of Administration Six Hours After Administration
Time: day 1 of protocol therapy
Description: Serum concentration of alisertib on the fourth day of administration prior to the administration of the day 4 dose in nanograms/milliliter.
Measure: Serum Concentration of Alisertib on the Fourth Day of Administration Prior to the Administration of the Day 4 Dose
Time: day 4 of protocol therapy
Description: Serum concentration of alisertib on the seventh day of administration prior to the administration of the day 7 dose in nanograms/milliliter.
Measure: Serum Concentration of Alisertib on the Seventh Day of Administration Prior to the Administration of the Day 7 Dose.
Time: day 7 of protocol therapy
HPO Nodes
Genes 40
KCNAB2 PMS1 GABRD MLH1 NUTM1 KRAS RAF1 TGFBR2 MSH6 RPS20 BMPR1A PMS2 MSH2 PTPN11 MLH3 RERE SEMA4A NF1 RET RUNX1 NME1 GPC3 BRAF PHOX2B SKI MAPRE2 EPCAM PRDM16 PIK3CA GDNF ASCL1 PALB2 MYO1H BDNF EDN3 BRD4 SDHB FAN1 GPC4 TUBB Genes 99
FOXE1 CDKN1B CDKN1C VHL SOX9 H19-ICR HNF1A HNF1B POU6F2 DIS3L2 WWOX NRAS HDAC4 FN1 MAX KIF1B SRC WRN GATA4 WT1 APC NSD1 SRY TSC1 TSC2 EXT2 MSH2 KEAP1 MINPP1 REST RET DCC MDH2 PTCH1 PTEN HNF4A AAGAB TMEM127 TRIP13 OGG1 DICER1 ALX4 PALB2 PHF21A MAP3K1 TFE3 ZFPM2 AXIN2 BAP1 NOD2 TBX18 MET STK11 MSH6 KLLN IGF2 DLC1 DMRT3 GPC3 LMNA BRCA2 SDHAF2 PIK3CA PRCC TRIM28 SETBP1 BUB1 SLC49A4 BUB1B VAMP7 NR0B1 GPC4 MLH1 FIBP KCNQ1 FLCN COL14A1 AKT1 HABP2 NR5A1 FGFR3 PAX6 CDC73 BMPER CTNNB1 FH BUB3 RNF139 CEP57 KCNQ1OT1 TRIM37 EP300 SEC23B H19 SDHA TP53 SDHB SDHC SDHD Genes 41
KCNAB2 PMS1 GABRD MLH1 NUTM1 KRAS RAF1 TGFBR2 FLI1 MSH6 RPS20 BMPR1A PMS2 MSH2 PTPN11 MLH3 RERE SEMA4A NF1 RET RUNX1 NME1 GPC3 BRAF PHOX2B SKI MAPRE2 EPCAM PRDM16 PIK3CA GDNF ASCL1 PALB2 MYO1H BDNF EDN3 BRD4 SDHB FAN1 GPC4 TUBB Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS Genes 116
VEGFC CDKN1A CDKN1B FOXO1 CDKN2A KRAS CDKN2B CDKN2C GDF5 FLNA ATP6V1B2 PMS2 FLT4 NRAS KRT17 PDGFB PDGFRA RB1 PDGFRB SRC MC1R WRN WT1 APC CASP10 NBN GJC2 NR4A3 RPS19 TSC1 TSC2 EWSR1 EXT1 EXT2 MSH2 KEAP1 IDH1 IDH2 REST DCC PTCH1 PTEN MDM2 FAS FASLG SSX1 SSX2 TRIP13 DICER1 PTH1R AXIN2 MEN1 NUTM1 TBX18 SLC22A18 MSH6 RASGRP1 FAM20C BMPR1A BMPR1B KLLN PTPN11 DLC1 MTAP NF1 ANTXR2 LMNA BRAF NF2 ABCA5 PIK3CA KCNH1 ELMO2 SQSTM1 BRD4 DHCR24 RECQL4 BUB1 BUB1B CHEK2 HRAS PTCH2 MLH1 PRKAR1A FLCN PRKCD SPRED1 AKT1 ASPSCR1 TAF15 FGFR3 PAX3 PLCD1 CDC73 GREM1 PAX7 GNAS CTNNB1 FH BUB3 SUFU MAP2K1 CEP57 KIT EP300 PRLR SEC23B SDHA TP53 NOTCH3 SDHB SDHC SDHD COL1A1 SOS1 FOXC2 Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18 Genes 4
EWSR1 BRD4 NUTM1 RB1 Genes 29
MPL MLF1 NSD1 JAK2 KRAS NPM1 ELANE DKC1 ETV6 TCIRG1 DNAJC21 SRP54 EFL1 FLT3 NUP214 CEBPA THPO MLLT10 RUNX1 PIGA CBFB BRCA2 KIT PICALM SBDS GFI1 SH3GL1 LPP DNMT3A Genes 21
BUB3 HRAS FOXO1 MLH1 CEP57 TRIP13 SLC22A18 NBN MSH6 DICER1 PMS2 MSH2 PAX3 KEAP1 PAX7 BUB1 NF1 BUB1B MC1R NRAS PTCH1 Genes 11
CHEK2 LMNA MDM2 CDKN2A RB1 TP53 RECQL4 MTAP SQSTM1 WRN RPS19 Genes 61
PMS1 GABRD CDKN2A NUTM1 KRAS RAF1 TGFBR2 FLI1 MSH6 ERBB2 BMPR1A PMS2 PTPN11 MLH3 IGF2 NF1 GPC3 BRAF NF2 RB1 PIK3CA ASCL1 MYO1H BRD4 SETBP1 GPC4 TUBB CHEK2 KCNAB2 APC MLH1 LRP5 NBN C11ORF95 RPS20 TSC1 TSC2 RELA MSH2 MSH3 RERE KEAP1 IDH1 IDH2 SEMA4A RET RUNX1 NME1 PHOX2B SKI MAPRE2 EPCAM PRDM16 GDNF DICER1 PALB2 BDNF EDN3 H19 SDHB FAN1 Genes 57
CDKN1C SOX9 H19-ICR SLC22A18 STK11 SETD2 POU6F2 IGF2 DIS3L2 DMRT3 WWOX HDAC4 GPC3 BRCA2 RB1 MNX1 PIK3CA TRIM28 SETBP1 APC2 BUB1 BUB1B VAMP7 NR0B1 GPC4 CHEK2 GATA4 WT1 APC NSD1 FIBP KCNQ1 SRY EXT2 NR5A1 FGFR3 MSH3 PAX6 CDC73 BMPER REST PTCH1 BUB3 CEP57 TRIP13 KIT KCNQ1OT1 DICER1 SLC37A4 TRIM37 ALX4 PALB2 H19 PHF21A TP53 MAP3K1 ZFPM2 Genes 762
CDKN1A CDKN1B CDKN1C CDKN2A HFE CDKN2B CDKN2C GDF5 TSR2 CDKN2D H19-ICR TMEM67 RPL26 RPL27 TREX1 ASXL1 ERBB2 SCN11A POU6F2 ERCC2 RPL35A ERCC3 BRIP1 ERCC4 ABL1 ERCC5 CEBPA ERCC6 PDE6D GCM2 CEL PDGFB PDGFRA PDGFRL MNX1 PDGFRB LEMD3 ENPP1 CTSC ESR1 HLA-DRB1 SLC26A4 MAX APC2 RPS7 TMC6 TMEM216 TRPS1 ACTB RPS10 MC1R MC2R BLNK RPS14 RPS15A ACTG2 ETV6 TCIRG1 DNAJC21 EVC HMBS L2HGDH RPS17 MCM4 RPS19 RPS20 TSC1 TSC2 EWSR1 EXT1 EXT2 RPS24 RPS26 RPS27 ACVR1 EYA1 RPS28 RPS29 MAGT1 ACVRL1 MDH2 MDM2 ADA HNF4A ADAR TRIP13 LYST PICALM ALX4 F13A1 TERF2IP PHF21A F13B RYR1 MAP3K1 AXIN1 TBC1D24 AXIN2 BAP1 CHRNG TWIST1 MEN1 TNFRSF4 FANCA FANCC FANCD2 FANCE TYR GFI1B FAH MET TYROBP FANCB FANCF FANCG SERPINA1 ARID1B SAMD9L AP2S1 MGAT2 DLC1 ICOS DMRT3 SFTPA2 PIGA MGMT MBTPS2 CLCNKB HOXD13 PIK3CA PIK3R1 ACAN FDPS HPGD JAG1 RNASEH2C RECQL4 SCN4A HACE1 RAD54B NR0B1 MITF AHCY GPC4 SCN9A SCN10A HRAS MLF1 MLH1 CTHRC1 TJP2 GTF2H5 FGF3 CC2D2A ANTXR1 LMOD1 PLAG1 FGF8 COL14A1 AKT1 NOP10 ASPSCR1 FGFR1 PLCB4 FGFR3 PLCD1 FGFR2 HAX1 MMP1 MAD2L2 UROD FH MN1 ALK HSPA9 SEC23B SEC23A CARD14 SDHA RAD54L SDHB SDHC SDHD FOXI1 COL1A1 FOXC2 COL2A1 FOXE1 MPL VEGFC ALX3 PMS1 FOXO1 VHL COL4A5 FLI1 MRE11 HSPG2 FLNA KLF11 COL7A1 PIGL SEMA3C BIN1 FLT3 PMS2 FLT4 COL11A2 CIB1 CCDC22 WAS COMP FN1 WIPF1 OFD1 KLF6 ADAMTS3 RNASEH2A LIN28B SFTPC CTC1 PUF60 WHCR NSD2 PPM1D NELFA MAP3K8 INPP5E POLD1 POLE WNT5A POLH GNPTAB SH3GL1 POT1 SH3KBP1 FERMT1 POLR1C WRN TUBB KCNAB2 WT1 APC IKBKG SHH PORCN SHOX BIRC3 POU2AF1 XIAP NLRP1 SAMHD1 XPA MSH2 CHD7 XPC MSH3 ZSWIM6 IDH1 MINPP1 IDH2 TMEM107 TXNRD2 XRCC2 XRCC4 SIX1 SIX3 FANCM SKI FAS FCN3 NHP2 FASLG CR2 CTSA TMEM127 CREB1 CREBBP AR ZAP70 ABCC6 CRKL ZIC2 FAN1 MSR1 MST1 PPP2R1B SETD2 C2CD3 MLH3 PIEZO2 IGF2 ARSA IGF2R MTAP MMEL1 STS GNA14 PMVK SLC12A3 COX1 COX2 UBE2T COX3 IGH SLC17A9 DYNC2LI1 PRCC ELMO2 ASCL1 PRF1 TP63 SLCO2A1 IGHM MTM1 ND1 SETBP1 ND4 ND5 ND6 SNAI2 PTCH2 RNR1 MPLKIP PRKAR1A SMARCB1 ABCB11 WNT10A FLCN SMARCD2 APPL1 PRKCD FOXP1 TRNF C11ORF95 CTBP1 SMO NR5A1 TRNH CTLA4 TRNK IGLL1 TRNL1 ATM RERE MAPK1 CTNNB1 TRNP TRNQ TRNS1 TRNS2 TRNW KDSR SUFU MAP2K1 MAP2K2 CEP57 FZD2 PRDM16 IL2RG G6PC SLC37A4 STAG3 PALLD TRIM37 SLX4 PRLR MUTYH H19 MVD IL7 MVK IL7R SOS1 MYC SOX2 GABRD CYLD MYCN TET2 SOX9 MYD88 IL12A IL12RB1 MYF6 TCTN3 ATP6V1B2 INTU MYH8 MYH11 SAMD9 ATP7A DIS3L2 ATP7B PSAP WWOX MYLK HDAC4 ATR SPIB ACD ATRX SPINK1 ING1 TNFSF12 RTEL1 INHBA PSENEN INS GJB4 CYP11B1 CYP11B2 GJB6 ARHGAP26 KIF1B MAFA RNF113A SRC GAS1 GATA1 CPLX1 GATA2 GATA4 PDX1 BARD1 GBA CDH23 SRP54 FGFRL1 IRF1 NBN SRP72 IRF5 DAXX SRY GCGR CCND1 BCL2 SMARCAD1 GCK NDP KEAP1 TNFRSF10B BCL6 RB1CC1 DCC GPR101 PTCH1 PTEN GDF2 SSX1 BCR SSX2 ADA2 NSUN2 NEK9 DDB2 GDNF DPM1 GINS1 RNF43 GFI1 PTH1R STAR BDNF NAGS STAT1 ITK STAT3 KIAA0753 NOD2 BLK BLM NUTM1 JAK2 STK4 IFIH1 GJA1 STK11 MALT1 NEK1 PTPN3 FAM20C BMPR1A BMPR1B GJB2 GJB3 CCM2 PTPN11 ARL6IP6 KARS NEUROD1 NF1 ANTXR2 DHH GPC3 BRCA1 BRAF BRCA2 NF2 TINF2 SDHAF2 WASHC5 KCNH1 CXCR4 SQSTM1 GLI1 GLI2 GLI3 ABCC8 NBEAL2 DHCR7 DHCR24 KCNJ10 NFKB1 BTK KCNJ11 NFKB2 BUB1 CYP26C1 BUB1B VAMP7 TMC8 MFN2 DKC1 KCNQ1 C1S GNA11 KDR TRPV3 BCL10 DLEC1 GNAI3 GNAQ CDC73 BMPER GNAS SEMA4A GNB1 NME1 TMEM231 FOXH1 PHOX2B CPLANE1 MAPRE2 NODAL TAL1 KIT TAL2 KCNQ1OT1 TNFSF15 DNASE1L3 NOTCH1 NOTCH3 KIF11 CDON DNM2 DNMT3A PNP RAD21 TBX2 RAD51 RAD51C RNASEH2B RAD51D KRAS NPM1 RAF1 KRT1 RAG1 RAG2 CACNA1S KRT5 TCF4 KRT6B EFL1 HNF1A FAT4 HNF1B KRT9 TCF3 CYSLTR2 KRT10 KRT14 EVC2 KCNE3 RARA RPGRIP1L KRT16 CARMIL2 NRAS SRD5A3 KRT17 SASH1 RASA1 RHBDF2 SH2B3 USB1 RB1 TCOF1 NRTN DOCK8 DYNC2H1 CALR GPR35 SLC26A2 NTHL1 NTRK1 MYO1H NUMA1 DVL1 ASCC1 DVL3 NSD1 LAMA3 AGGF1 GPR143 CASP8 B3GALT6 LAMB3 CASP10 GJC2 NR4A3 CASR LAMC2 FANCL RELA OCA2 TDGF1 NUP214 OCRL AIP REST RET MLLT10 RUNX1 WRAP53 CBFB ECE1 GPC6 DLL1 TEK CBL TERC ECM1 AAGAB TERT OGG1 TFAP2A DICER1 WDPCP PALB2 EDN1 LETM1 OPCML MSTO1 EDN3 EDNRB TFE3 ZFPM2 RFWD3 KRIT1 KIF7 SIX6 TG RAD50 ESCO2 VANGL2 RMRP TBX18 TGFBR2 POLR1D SLC22A18 TGIF1 MSH6 COL18A1 USP8 RASGRP1 LIG4 SEMA3D GTF2E2 KLLN RNASEL THPO SF3B1 HMGA2 ALX1 LMNA RNF6 CD19 MS4A1 MTMR14 EGFR LMO1 DCLRE1C ABCA5 LZTS1 LMX1B CD27 TRIM28 CD28 VANGL1 CCBE1 SBDS FANCI BRD4 SLC25A13 MRAP ARMC5 LPP SLC49A4 CHEK2 TREM2 TNFRSF13C FIBP LRRC8A ELANE TNFRSF13B LRP5 CD70 SPRED1 CD79A CD79B CD81 SLC45A2 PRKN PARN HABP2 TAF15 PAX3 EIF2AK4 PAX4 RPL35 PAX6 GREM1 PAX7 SPRTN TNFRSF1B BUB3 KAT6B HBB PDCD10 RNF139 SH2D1A ENG CDH1 EPCAM RSPO1 NNT RPL5 TNPO3 CD96 EP300 DISP1 TOP2A TP53 RPL10 RPL11 SMAD4 RPL15 CDK4 RPL18 Genes 2
SLC22A18 DICER1 Genes 11
APC CDKN1C H19 SETBP1 KCNQ1OT1 KCNQ1 H19-ICR IGF2 SLC37A4 GPC4 GPC3