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Report for Clinical Trial NCT03787056

Developed by Shray Alag, 2020.
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:Glioblastoma Endometrial Neoplasms Kidney Neoplasms Liver Neoplasms Carcinoma, Hepatocellular
HPO:Endometrial carcinoma Glioblastoma multiforme Hepatocellular carcinoma Neoplasm of the liver 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
Group Labels: 1

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

Allocation: N/A

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: