SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03213652

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Ensartinib in Patients With Tumors Harboring ALK or ROS1 Genomic Alterations

This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back or do not respond to treatment and have spread to other places in the body. Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT03213652 Advanced Malignant Solid Neoplasm ALK Fusion Protein Expression ALK Gene Mutation ALK Gene Translocation Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma Histiocytosis Recurrent Childhood Central Nervous System Neoplasm Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Refractory Central Nervous System Neoplasm Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma ROS1 Fusion Positive ROS1 Gene Mutation ROS1 Gene Translocation
MeSH: Lymphoma Neoplasms Lymphoma, Non-Hodgkin Neuroblastoma Histiocytosis Nervous System Neoplasms Central Nervous System Neoplasms
HPO: Histiocytosis Lymphoma Neoplasm Neoplasm of the central nervous system Neoplasm of the nervous system Neuroblastoma Non-Hodgkin lymphoma

3 Interventions

Name: Ensartinib

Description: Given PO

Type: Drug

Treatment (ensartinib)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Treatment (ensartinib)

Name: Pharmacological Study

Description: Correlative studies

Type: Other

Treatment (ensartinib)


Primary Outcomes

Description: A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.

Measure: Objective response rate

Time: Up to 4 years

Secondary Outcomes

Description: Incidence of toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

Measure: Incidence of toxicity

Time: Up to 4 years

Description: PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.

Measure: Progression free survival (PFS)

Time: From the initiation of protocol treatment to the occurrence of disease progression or disease recurrence or death from any cause, assessed up to 4 years

Other Outcomes

Description: A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Measure: Pharmacokinetic (PK) parameters

Time: Pre-dose, 1, 2, 4, 6-8, and 20-24 hours post day 1 dose and pre-dose, 1, 2, 4, and 6-8 hours post day 28 dose of course 1

Description: Descriptive analysis will be performed and will be summarized with simple summary statistics.

Measure: Biomarkers as predictors of response to ensartinib

Time: Up to 4 years

Description: Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor DNA will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.

Measure: Changes in tumor genomic profile

Time: Up to 4 years

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 F1174L

EXPLORATORY OBJECTIVES: I. To evaluate other biomarkers as predictors of response to ensartinib and specifically, whether tumors that harbor different missense mutations or fusions (including the crizotinib resistant F1174L ALK variant) will demonstrate differential response to ensartinib treatment. --- F1174L ---



HPO Nodes


HPO:
Histiocytosis
Genes 2
IFNGR1 SLC29A3
Lymphoma
Genes 94
BLM MYC CDKN2A KRAS MYD88 RMRP RAG1 RAG2 MALT1 MSH6 RASGRP1 LIG4 TCF4 PMS2 ICOS NRAS WAS WIPF1 CD19 MS4A1 USB1 IGH TINF2 RB1 DCLRE1C TNFSF12 RTEL1 CTC1 CD27 CD28 PIK3R1 PRF1 NTHL1 TP63 POLE HLA-DRB1 NFKB1 NFKB2 RECQL4 RAD54B CHEK2 TNFRSF13C APC MLH1 TNFRSF13B DKC1 BIRC3 XIAP CASP10 NBN PRKCD COL14A1 FOXP1 CD81 PARN NOP10 CCND1 BCL10 BCL2 MSH2 CHD7 CTLA4 ATM BCL6 MAGT1 RUNX1 TNFRSF1B XRCC4 WRAP53 PTEN MDM2 FAS NHP2 ADA FASLG CR2 SH2D1A TERC AAGAB KIT TERT NSUN2 IL2RG LYST RNF43 ZAP70 DNASE1L3 TP53 RAD54L ITK STAT3 IL7R KIF11 PNP
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
Neoplasm of the central nervous system
Genes 116
ALX3 SOX2 PMS1 GABRD VHL CDKN2A KRAS RAF1 FLI1 TCTN3 ERBB2 FAT4 PMS2 PDE6D NRAS OFD1 PDGFB ADAMTS3 RB1 PDGFRB POLD1 NTHL1 MYO1H POLE MAX KIF1B TMEM216 WRN TUBB KCNAB2 WT1 APC NBN RPS20 TSC1 TSC2 EWSR1 RELA MSH2 MSH3 ZSWIM6 OCRL KEAP1 IDH1 IDH2 RET RUNX1 MDH2 PTCH1 PTEN SKI TMEM127 GDNF DICER1 WDPCP PALB2 BDNF EDN3 KRIT1 BAP1 KIAA0753 KIF7 FAN1 SIX6 NUTM1 TGFBR2 MSH6 BMPR1A CCM2 KLLN PTPN11 MLH3 NF1 ALX1 GPC3 LMNA BRAF NF2 SDHAF2 PIK3CA ASCL1 CCBE1 GLI3 BRD4 ARMC5 SETBP1 GPC4 CHEK2 PTCH2 MLH1 SMARCB1 LRP5 AKT1 C11ORF95 FGFR1 RERE GNAS SEMA4A CTNNB1 NME1 FH PHOX2B CPLANE1 PDCD10 SUFU MAPRE2 EPCAM PRDM16 MN1 SEC23B SDHA TP53 NOTCH3 SDHB SDHC SDHD
Neoplasm of the nervous system
Genes 143
ALX3 SOX2 CDKN1A PMS1 CDKN1B GABRD VHL CDKN2A KRAS MYCN CDKN2B RAF1 CDKN2C FLI1 TCTN3 ERBB2 FAT4 PMS2 PDE6D NRAS OFD1 ATRX PDGFB ADAMTS3 PDGFRA RB1 PDGFRB LIN28B POLD1 NTHL1 MYO1H POLE MAX KIF1B APC2 MAFA TMEM216 WRN TUBB KCNAB2 WT1 APC NSD1 L2HGDH NBN DAXX RPS20 TSC1 TSC2 EWSR1 GCGR RELA MSH2 MSH3 ZSWIM6 OCRL KEAP1 IDH1 IDH2 RET RUNX1 MDH2 PTCH1 PTEN MDM2 SKI TMEM127 GDNF DICER1 RNF43 WDPCP PALB2 BDNF EDN3 KRIT1 BAP1 KIAA0753 KIF7 MEN1 FAN1 SIX6 NUTM1 TGFBR2 MSH6 SETD2 BMPR1A CCM2 KLLN PTPN11 MLH3 KARS NF1 ALX1 GPC3 LMNA BRAF NF2 LMO1 SDHAF2 PIK3CA ASCL1 CCBE1 GLI3 BRD4 ARMC5 SETBP1 HACE1 GPC4 CHEK2 HRAS PTCH2 MLH1 PRKAR1A SMARCB1 LRP5 SPRED1 AKT1 C11ORF95 FGFR1 RERE GNAS SEMA4A CTNNB1 NME1 FH PHOX2B CPLANE1 PDCD10 SUFU MAPRE2 KIT EPCAM PRDM16 MN1 ALK TOP2A SEC23B SDHA TP53 NOTCH3 SDHB SDHC SDHD
Neuroblastoma
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
Non-Hodgkin lymphoma
Genes 22
MYC FAS ADA FASLG IGH KIT BIRC3 CASP10 NBN CD28 MALT1 PRKCD RASGRP1 FOXP1 PIK3R1 NTHL1 POLE CCND1 BCL10 CTLA4 ATM TNFRSF1B