SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03787056

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients

Progastrin is a pro-hormone that, in physiological conditions, is maturated in gastrin in G cells of the stomach. The role of the gastrin is to stimulate the secretion of gastric acids during digestion. It is also important for the regulation of cell growth of the gastric mucosal. In a healthy person, progastrin is not detectable in the peripheral blood. However, progastrin is abnormally released in the blood of patients with different cancers (colorectal, gastric, ovarian, breast, cervix uterus, melanoma…) The gene GAST coding for progastrin is a direct target gene of the WNT/ß-catenin oncogenic pathway. The activation of this oncogenic pathway is an early event in cancer development. Chronic activation of the WNT/ß-catenin oncogenic pathway occurs in almost all human solid tumors and is a central mechanism in cancer biology that induces cellular proliferation, blocking of differentiation leading to primary tumor growth and metastasis formation. Progastrin measured in the peripheral blood of patients on treatments, could be a new powerful marker for diagnosis and prognosis at different stages.

NCT03787056 Cancer Breast Cancer Gastric Cancer Renal Cancer Prostate Cancer Melanoma Lung Cancer Hepatocellular Cancer Colorectal Cancer Head and Neck Cancer Pancreatic Cancer Ovarian Cancer Glioblastoma Endometrial Cancer Bladder Cancer Esophageal Cancer B-cell Lymphoma
MeSH: Colorectal Neoplasms Pancreatic Neoplasms Glioblastoma Lymphoma, B-Cell Head and Neck Neoplasms Urinary Bladder Neoplasms Esophageal Neoplasms Endometrial Neoplasms Kidney Neoplasms Carcinoma, Renal Cell Liver Neoplasms Carcinoma, Hepatocellular
HPO: B-cell lymphoma Bladder neoplasm Clear cell renal cell carcinoma Endometrial carcinoma Esophageal neoplasm Glioblastoma multiforme Hepatocellular carcinoma Neoplasm of head and neck Neoplasm of the large intestine Neoplasm of the liver Neoplasm of the pancreas Papillary renal cell carcinoma Renal cell carcinoma Renal neoplasm

1 Interventions

Name: Blood draws

Description: Blood draws are realized at each steps of patient disease management. The volume of each blood drawn is 20 mL for progastrin measurements and additional 5 mL for the dosage of the other tumor markers (PSA, CA19-9, CA125…). The frequency of blood drawn is maximum every 3 weeks (i.e. in case of chemotherapy treatment) and minimum every 6 months (for patients in follow up)

Type: Other

Cancer patients


Primary Outcomes

Description: Progastrin concentration in plasma samples will be measured with an ELISA Kit (CancerREAD LAB) provided by ECS Progastrin.

Measure: ROC curve AUC regarding diagnostic accuracy of progastrin levels at baseline in cancer patients compared to non-cancer controls

Time: At baseline

Secondary Outcomes

Description: A nonlinear mixed effect model will be used to model the progastrin measurements done during treatments and follow-up of patients.The effect of each event (chemotherapy, surgery…) on the progastrin value and in the inter-individual variability of production and/or elimination rates of progastrin will be analyzed. Progastrin will be measured by ELISA, and the values will be expressed in pM. Measures will be done depending on the treatment received. Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients.

Measure: Longitudinal kinetic of progastrin values during treatments, assessed by modeled kinetic parameters of interest

Time: 6 years

Description: 24 patients will be selected, upon their agreement and serum high levels, to enter in nychtemer (12 patients) or weekly (12 patients) cohorts. For the Nychtemer cohort, progastrin will be assayed at d1 at 8:00 am; 11:00 am; 2:00 pm; 5:00 pm; 8:00 pm and at d2 at 8:00 For the weekly cohort, progastrin will be assayed Day 1; Day 8; Day 15 and +/- Day 22; ideally on the same hour times. Progastrin will be measured by ELISA, and the values will be expressed in pM.

Measure: Nycthemeral and weekly progastrin variations

Time: every 3 hours within 24 hours for the Nycthemeral cohort, and every week for 2 or 3 weeks for the weekly cohort

Description: A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (hepatic function, as measured by the concentration of AST, ALT and bilirubin). Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients

Measure: Determinants of progastrin serum values: hepatic function

Time: 6 years

Description: A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (renal function, as measured by creatinin concentration and creatinin clearance). Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients

Measure: Determinants of progastrin serum values: renal function

Time: 6 years

Description: A nonlinear mixed effect model will be used to correlate the individual characteristics of the patient (age and gender) with progastrin concentration at the inclusion.

Measure: Determinants of progastrin serum values: age

Time: at the inclusion

Description: A nonlinear mixed effect model will be used to correlate genders with progastrin concentrations at the inclusion.

Measure: Determinants of progastrin serum values: gender

Time: at the inclusion

Description: The relationships between the progastrin kinetics during and after treatment and overall survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment. Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.

Measure: Overall survival

Time: 6 years

Description: The relationships between the progastrin kinetics during and after treatment and recurrence free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment. Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.

Measure: recurrence free survival

Time: 6 years

Description: The relationships between the progastrin kinetics during and after treatment and progression free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment. Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.

Measure: progression free survival

Time: 6 years

Description: The size of the tumor will be correlated to progastrin concentration at the time of cancer diagnosis

Measure: The tumor size at cancer diagnosis

Time: At baseline

Description: The ability of progastrin kinetics during the neoadjuvant period to predict the outcome of the surgery (complete or not) will be analyzed by a ROC curve. If applicable.

Measure: Complete surgery

Time: 6 years

Description: The ability of the progastrin kinetics to predict recurrence free survival (curative cohorts), will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up.

Measure: time to recurrence (for patients enrolled in curative intent cohorts).

Time: 6 years

Description: The ability of the progastrin kinetics to predict progression-free survival (non-curative cohorts) will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up

Measure: time to progression (for patients enrolled in non-curative intent cohorts)

Time: 6 years

Description: The ability of the progastrin kinetics to predict time to death will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up

Measure: time to death (whenever it occurred)

Time: 6 years

Description: The ROC AUC will be compared between classical markers and the prograstrin. Logistic regression will be used to combine the classical marker(s) and the progastrin in order to estimate the diagnostic value of the marker combination. progastrin, CA15-3, CA19-9, CA125, CEA, PSA and AFP concentration will be measured on blood sample taken at the inclusion.

Measure: Comparison of the initial values and of the kinetics of other serum tumor markers (CA15-3, CA 19-9, CA125, CEA, PSA, AFP) with those of progastrin

Time: at the baseline

Purpose: Diagnostic

Single Group Assignment


There is one SNP

SNPs


1 V600E

Lung carcinoma: - SCLC for curative-intent cohort - Stage IV NSCLC with EGFR activating mutation, BRAF V600E mutation, ALK or ROS1 fusion. --- V600E ---



HPO Nodes


HPO:
B-cell lymphoma
Genes 15
FAS ADA FASLG IGH BIRC3 CASP10 NBN MALT1 PRKCD RASGRP1 FOXP1 PIK3R1 CCND1 BCL10 ATM
Bladder neoplasm
Genes 22
PTEN HRAS APC KRAS RB1 AAGAB FLCN PIK3CA COL14A1 RNF43 AKT1 EP300 NTHL1 FGFR3 AXIN2 ATP7A SRC CTNNB1 DLC1 BUB1B NRAS DCC
Clear cell renal cell carcinoma
Genes 1
NOD2
Endometrial carcinoma
Genes 19
PTEN MLH1 CDH1 PIK3CA MSH6 AKT1 POLD1 BMPR1A NTHL1 POLE SEC23B PMS2 MSH2 KLLN MSH3 SDHB SDHC SDHD GREM1
Esophageal neoplasm
Genes 18
ASCC1 MSR1 RNF6 RHBDF2 APC PDGFRA CTHRC1 KIT TGFBR2 STK11 DLEC1 STAT1 SDHA SDHB SDHC WWOX RAD21 FH
Glioblastoma multiforme
Genes 16
PMS1 APC MLH1 KRAS EPCAM TGFBR2 PIK3CA MSH6 ERBB2 RPS20 BMPR1A PMS2 MSH2 MLH3 SEMA4A FAN1
Hepatocellular carcinoma
Genes 54
PMS1 HFE KRAS MST1 FAH IL12A TGFBR2 MET IL12RB1 MSH6 RASGRP1 TCF4 BMPR1A SERPINA1 PMS2 MLH3 IGF2 IGF2R MMEL1 ATP7B SPIB PDGFRL PIK3CA GPR35 SLC25A13 JAG1 AHCY APC MLH1 TJP2 ABCB11 CASP8 HMBS POU2AF1 CASP10 PRKCD IRF5 RPS20 MSH2 SEMA4A CTNNB1 SPRTN UROD FAS FASLG EPCAM G6PC TNFSF15 SLC37A4 TNPO3 H19 TP53 AXIN1 FAN1
Neoplasm of head and neck
Genes 21
ASCC1 FOXE1 MSR1 RNF6 RHBDF2 APC PDGFRA CTHRC1 KIT TGFBR2 STK11 HABP2 DLEC1 STAT1 SDHA SDHB SDHC MINPP1 WWOX RAD21 FH
Neoplasm of the large intestine
Genes 71
FOXE1 PMS1 CDKN2A KRAS MST1 TGFBR2 STK11 MSH6 TCF4 BMPR1A PMS2 KLLN MLH3 DLC1 NRAS BRCA1 BRCA2 PDGFRA DOCK8 PIK3CA GPR35 POLD1 NTHL1 POLE SRC BUB1 SH3KBP1 BUB1B CHEK2 APC MLH1 PRKAR1A FLCN COL14A1 AKT1 RPS19 RPS20 HABP2 MSH2 FGFR3 MSH3 KEAP1 GREM1 MINPP1 SEMA4A CTNNB1 DCC BUB3 PTEN MDM2 CEP57 ENG AAGAB TRIP13 KIT EPCAM DICER1 RNF43 PALLD EP300 PALB2 SEC23B MUTYH SDHA TP53 SDHB SDHC SDHD AXIN2 SMAD4 FAN1
Neoplasm of the liver
Genes 94
BLK PMS1 CDKN1C CDKN2A HFE KRAS MST1 FAH IL12A TGFBR2 H19-ICR MET TMEM67 IL12RB1 MSH6 RASGRP1 TCF4 KLF11 HNF1A BMPR1A POU6F2 SERPINA1 PMS2 MLH3 NEUROD1 IGF2 IGF2R DIS3L2 RPGRIP1L MMEL1 ATP7B GPC3 BRCA1 CEL SPIB BRCA2 PDGFRL PIK3CA TRIM28 GPR35 INS INPP5E ABCC8 SLC25A13 JAG1 KCNJ11 SETBP1 AHCY GPC4 WT1 PDX1 APC MLH1 PRKAR1A TJP2 ABCB11 KCNQ1 CC2D2A CASP8 HMBS POU2AF1 CASP10 APPL1 PRKCD C11ORF95 IRF5 RPS20 RELA MSH2 GCK PAX4 REST SEMA4A CTNNB1 SPRTN UROD FAS HBB FASLG HNF4A TRIP13 KCNQ1OT1 EPCAM G6PC TNFSF15 SLC37A4 PALLD TNPO3 PALB2 H19 TP53 AXIN1 SMAD4 FAN1
Neoplasm of the pancreas
Genes 80
RAD51 RAD51C CDKN1A PMS1 CDKN1B RAD51D VHL CDKN2A NUTM1 KRAS CDKN2B CDKN2C CDKN2D TGFBR2 FLI1 MRE11 STK11 MSH6 BMPR1A PMS2 MLH3 BRIP1 MGMT SLC12A3 BRCA1 ACD SPINK1 BRCA2 USB1 CLCNKB TINF2 RTEL1 PDGFRB CTC1 PIK3CA NTHL1 BRD4 POT1 MAFA MC1R MITF CHEK2 WT1 APC BARD1 MLH1 PRKAR1A DKC1 NBN COL14A1 RPS20 TSC1 PARN NOP10 TSC2 EWSR1 GCGR MSH2 CDC73 SEMA4A WRAP53 PTEN MDM2 NHP2 TERC AAGAB TERT EPCAM RNF43 PALLD PALB2 TERF2IP TP53 NOTCH3 SMAD4 BAP1 CDK4 MEN1 FAN1 RAD50
Papillary renal cell carcinoma
Genes 8
FOXE1 LMNA HABP2 CDC73 MET MINPP1 PRCC FH
Renal cell carcinoma
Genes 52
FOXE1 VHL MET STK11 HNF1A HNF1B KLLN DLC1 NRAS FN1 LMNA SDHAF2 PIK3CA PRCC MAX KIF1B SRC SLC49A4 BUB1B APC FLCN COL14A1 AKT1 TSC1 TSC2 HABP2 FGFR3 CDC73 KEAP1 MINPP1 CTNNB1 RET DCC FH MDH2 PTEN RNF139 HNF4A AAGAB TMEM127 OGG1 DICER1 EP300 SEC23B SDHA SDHB TFE3 SDHC SDHD AXIN2 BAP1 NOD2
Renal neoplasm
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