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

Not Applicable

Recruiting

• Conditions: Lung Cancer; Renal Cancer; Endometrial Cancer; Breast Cancer; Hepatocellular Cancer; Head and Neck Cancer; Pancreatic Cancer; Ovarian Cancer; Glioblastoma; Cancer
• Interventions: Other: Blood draws

• Registration Number: NCT03787056
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-26
• Study Start: 2018-12-04
• Study First Submitted QC: 2018-12-20
• Study First Posted: 2018-12-26
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-12
• Last Update Posted: 2021-07-16
• Primary Completion: 2028-01-04
• Study Completion: 2028-01-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 410

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cancer patients	Blood draws	420 patients affected by different types of cancer and treated in a curative or a palliative intent. In total 17 cohorts will be open, including: breast cancer, head and neck carcinomas, renal cell carcinoma, prostate carcinoma, lung carcinoma, hepatocellular carcinoma, colorectal carcinoma, thyroid cancer, pancreatic adenocarcinoma, ovarian adenocarcinoma, glioblastoma, endometrial adenocarcinoma, bladder carcinoma, oesophago-gastric carcinoma, B-cell lymphoma, gastric carcinomas. Patients enrolled in curative intent treatment cohorts will never have been previously treated for their cancer. Patients enrolled in non-curative intent treatment cohorts will have never been treated for their metastatic cancers previously, or have developed advanced/metastatic diseases as relapses of localized cancers previously treated with curative intent therapeutic strategies. Other cohort will be open (stability cohorts) : nychtemer cohort and post-operative kinetic cohort.

Primary Outcome Measures

Name	Time	Method
ROC curve AUC regarding diagnostic accuracy of progastrin levels at baseline in cancer patients compared to non-cancer controls	At baseline	Progastrin concentration in plasma samples will be measured with an ELISA Kit (CancerREAD LAB) provided by ECS Progastrin.

Secondary Outcome Measures

Name	Time	Method
Longitudinal kinetic of progastrin values during treatments, assessed by modeled kinetic parameters of interest	6 years	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.
Nycthemeral and weekly and post-operative progastrin variations	every 3 hours within 24 hours for the Nycthemeral cohort, and every week for 2 or 3 weeks for the weekly cohort	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.
Determinants of progastrin serum values: hepatic function	6 years	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
Determinants of progastrin serum values: renal function	6 years	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
Determinants of progastrin serum values: age	at the inclusion	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.
Determinants of progastrin serum values: gender	at the inclusion	A nonlinear mixed effect model will be used to correlate genders with progastrin concentrations at the inclusion.
Overall survival	6 years	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.
recurrence free survival	6 years	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.
progression free survival	6 years	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.
The tumor size at cancer diagnosis	At baseline	The size of the tumor will be correlated to progastrin concentration at the time of cancer diagnosis
Complete surgery	6 years	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 to recurrence (for patients enrolled in curative intent cohorts).	6 years	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 to progression (for patients enrolled in non-curative intent cohorts)	6 years	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 to death (whenever it occurred)	6 years	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
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	at the baseline	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.

Trial Locations

Locations (17)

Service de Pneumologie de l'hôpital de la Croix-Rousse; 🇫🇷 Lyon, France

Service d'Urologie de l'Hôpital E. Herriot; 🇫🇷 Lyon, France

Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE du Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service d'Hématologie de l'Hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service d'Oncologie médicale du Centre hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service de Gynécologie de l'hôpital de la Croix-Rousse; 🇫🇷 Lyon, France

Service d'Urologie de l'hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service de Gynécologie de l'hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service de Pneumologie du Groupement Hospitalier Est; 🇫🇷 Lyon, France

Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'Hôpital E. Herriot; 🇫🇷 Lyon, France

Service de NEURO-ONCOLOGIE du Groupement Hospitalier EST; 🇫🇷 Bron, France

Service d'Oto-Rhino-Laryngologie de l'Hôpital de la Croix-Rousse; 🇫🇷 Lyon, France

Service de Gynécologie du Groupement Hospitalier Est; 🇫🇷 Lyon, France

Service de Chirurgie de l'hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service de Dermatologie de l'hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, France

Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'hôpital de la Croix-Rousse; 🇫🇷 Lyon, France

Service de Pneumologie de l'Hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, France