SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01532011

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer

The goal of this clinical research study is to find the highest tolerable dose of the combination of erlotinib and pralatrexate that can be given to patients with advanced cancer. The safety of the drug combination will also be studied. Pralatrexate is designed to block the body's ability to make folic acid, a protein that may help cancer tissue to develop and spread. Erlotinib hydrochloride is designed to block proteins that are thought to cause cancer cells to grow. Erlotinib may help slow the growth of tumors.

NCT01532011 Advanced Cancers Solid Tumors
MeSH: Neoplasms
HPO: Neoplasm

2 Interventions

Name: Erlotinib

Description: Dose escalation group starting dose: 75 mg by mouth daily for a 28 day cycle. Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Type: Drug

Erlotinib + Pralatrexate

Name: Pralatrexate

Description: Dose escalation group starting dose: 15 mg/m2 by vein on days 1, 8, and 15 of a 28 day cycle. Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Type: Drug

Erlotinib + Pralatrexate


Primary Outcomes

Description: MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0. Grade 4 hematologic toxicity lasting 2 weeks or longer despite supportive care. Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE as attributable to therapy.

Measure: Maximum Tolerated Dose (MTD) of Erlotinib with Pralatrexate

Time: 8 weeks

Secondary Outcomes

Description: Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in tumor density, as measured in Hounsfield units (HU), by more than or equal to 15% (28).

Measure: Tumor Response

Time: 8 weeks

Purpose: Treatment

Single Group Assignment


There are 3 SNPs

SNPs


1 G719C

For the MTD expansion cohort, patients will be eligible if they meet one of the following criteria: I. Have an epidermal growth factor receptor (EGFR)-sensitive mutation (as G719C in exon 18, E746-A750 in exon 90, L858R in exon 21) and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR II. --- G719C ---


2 L858R

For the MTD expansion cohort, patients will be eligible if they meet one of the following criteria: I. Have an epidermal growth factor receptor (EGFR)-sensitive mutation (as G719C in exon 18, E746-A750 in exon 90, L858R in exon 21) and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR II. --- G719C --- --- L858R ---


3 T790M

Have an EGFR-resistant mutation (as T790M in exon 20), OR III. --- T790M ---



HPO Nodes


HPO:
Neoplasm
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