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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
410
Blood draws are realized at each steps of patient disease management. The volume of each blood drawn is 25 mL for progastrin measurements and 5 mL for the dosage of the other tumor markers. The frequency depend to the cancer and treatment administered : * Baseline at diagnosis : Local radical treatment : within 24h before surgery, within 24h after surgery and at the post-surgery follow up visit * Chemotherapy treatment : every 3 or 4 weeks * Radiotherapy : start day and at the end of radiation ("end of treatment" visit) * Palliative systemic treatment (only palliative cohorts) : every 3 to 12 weeks. Follow until the third progression or change of treatment line, or alternatively up to 5 years after inclusion * In case of PD or TOX * Follow up: at each visit scheduled (every 3 months) for the first 2 years, then every 6 months for 3 years * Relapse : withdrawn from the study and last progastrin measurement. Patient could be enrolled in the non-curative intent cohort
Service de NEURO-ONCOLOGIE du Groupement Hospitalier EST
Bron, France
RECRUITINGService d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'hôpital de la Croix-Rousse
Lyon, France
RECRUITINGService d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'Hôpital E. Herriot
Lyon, France
RECRUITINGService d'Oto-Rhino-Laryngologie de l'Hôpital de la Croix-Rousse
Lyon, France
RECRUITINGService d'Urologie de l'Hôpital E. Herriot
Lyon, France
RECRUITINGService de Gynécologie de l'hôpital de la Croix-Rousse
Lyon, France
RECRUITINGService de Gynécologie du Groupement Hospitalier Est
Lyon, France
RECRUITINGService de Pneumologie de l'hôpital de la Croix-Rousse
Lyon, France
RECRUITINGService de Pneumologie du Groupement Hospitalier Est
Lyon, France
RECRUITINGService d'Hématologie de l'Hôpital Lyon Sud
Pierre-Bénite, France
RECRUITING...and 7 more locations
ROC curve AUC regarding diagnostic accuracy of progastrin levels at baseline in cancer patients compared to non-cancer controls
Progastrin concentration in plasma samples will be measured with an ELISA Kit (CancerREAD LAB) provided by ECS Progastrin.
Time frame: At baseline
Longitudinal kinetic of progastrin values during treatments, assessed by modeled kinetic parameters of interest
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.
Time frame: 6 years
Nycthemeral and weekly and post-operative progastrin variations
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.
Time frame: every 3 hours within 24 hours for the Nycthemeral cohort, and every week for 2 or 3 weeks for the weekly cohort
Determinants of progastrin serum values: hepatic function
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
Time frame: 6 years
Determinants of progastrin serum values: renal function
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
Time frame: 6 years
Determinants of progastrin serum values: age
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.
Time frame: at the inclusion
Determinants of progastrin serum values: gender
A nonlinear mixed effect model will be used to correlate genders with progastrin concentrations at the inclusion.
Time frame: at the inclusion
Overall survival
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.
Time frame: 6 years
recurrence free survival
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.
Time frame: 6 years
progression free survival
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.
Time frame: 6 years
The tumor size at cancer diagnosis
The size of the tumor will be correlated to progastrin concentration at the time of cancer diagnosis
Time frame: At baseline
Complete surgery
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.
Time frame: 6 years
time to recurrence (for patients enrolled in curative intent cohorts).
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.
Time frame: 6 years
time to progression (for patients enrolled in non-curative intent cohorts)
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
Time frame: 6 years
time to death (whenever it occurred)
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
Time frame: 6 years
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
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.
Time frame: at the baseline
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