Informations générales (source: ClinicalTrials.gov)
Study of the Value of HPG80 (circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients with an NEM1 Mutation: the Progastrin-NEM1 Study (PRO-NEM1)
Observational
Centre Hospitalier Universitaire Dijon (Voir sur ClinicalTrials)
juin 2024
décembre 2026
05 avril 2025
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease with a high
degree of penetrance (>80% of patients). It is caused by the presence of the MEN1
mutation located on chromosome 11q13. The prevalence of this mutation is estimated at
approximately 1/30,000. This hereditary syndrome is characterized by the presence of
tumours of the endocrine system (adenoma of the parathyroid, pituitary and adrenal
glands, neuroendocrine tumors - NETs - of the endocrine pancreas, duodenum, lung or
thymus), which threaten the health of these patients. Other malignant tumors such as
breast cancer are also more common in patients with MEN1.
The clinical manifestations of MEN1 are linked to the location of the adenomas and NETs
and their secretory products. Indeed, most NETs produce and secrete numerous peptide
hormones (in the case of Insulinomas, Gastrinomas, VIPomas, Glucagonomas or PPomas for
example). This causes a specific clinical syndrome, which can be detected in the blood
serum. However, most NETs are "non-functional" tumors, which do not have specific
secretions.
Among general tumor markers, chromogranin A (CgA) is widely used as a biomarker for
monitoring NETs. CgA is a secretory protein released into the blood by neuroendocrine
cells. However, the performance of CgA as a diagnostic biomarker is too limited to be
used for the early identification of NETs, particularly in patients with MEN1.
This is why patients with MEN1 undergo regular biological and morphological examinations,
at least once a year, to screen for the development of adenomas and NETs. However, CgA or
hormone secretions assays, and imaging examinations (MRI, CT scan, or duodenopancratic
endoscopic ultrasound (EUS)) are tedious and stressful for patients; in addition, they
all have their limitations (poor performance for biological tests; irradiation for CT
scan; need for anesthesia for endoscopic ultrasound, etc.). Consequently, there is a need
for new markers to identify NETs in this population as early as possible.
Progastrin is a pro-hormone that, under physiological conditions, is matured into gastrin
in the G cells of the antrum of the stomach. The role of gastrin is to stimulate gastric
acid secretion during digestion. It also plays an important role in regulating cell
growth in the gastric mucosa. In pathological situations, it has been shown that the GAST
gene, which codes for progastrin, is over-expressed in human tumor cells of different
origins, leading to the accumulation of progastrin within them. Tumor cells that are
unable to mature progastrin into gastrin, either because the maturation enzymes are not
expressed or are inhibited, will secrete it. This circulating progastrin is then called
hPG80 (to differentiate it from intracellular progastrin) and is detectable in patient
blood. hPG80 is a new biomarker for the detection of different types of cancer. It
appears to be elevated in the early stages of the disease, potentially more so than other
biomarkers such as circulating tumor DNA (ctDNA) or NETest. In addition, hPG80 is easily
measured in plasma using the DxPG80.Lab ELISA (Progastrin Manufacturing). The analytical
characteristics of this CE-marked in vitro diagnostic test have been published in the
Analytical Methods journal. It has been validated in numerous studies of various cancers,
including NET patients. In addition, a study conducted by the team at Progastrin
Manufacturing (formerly ECS-Progastrin) showed that hPG80 was unequivocally present in
the peripheral blood of patients with 11 different types of cancer, with a concentration
significantly higher than that found in blood donors considered to be healthy. We
therefore hypothesize that hPG80 could also be a biomarker for NETs in MEN1.
Etablissements
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Chu Dijon Bourgogne - 21000 - Dijon - France | Côme LEPAGE | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patients with proven MEN1, symptomatic or not, confirmed on the basis of the
following international criteria (Thakker et al.):
- patients with an MEN1 mutation;
- patients belonging to an identified MEN1 family in which at least one first-degree
relative has been affected and has at least one MEN1-related lesion;
- patients without a positive genetic test or a family history of the disease, but
with at least two of the three main MEN1 lesions (parathyroid adenomas,
duodenopancreatic NETs and pituitary tumours).
- Majors patients,
- Patients who have undergone thoracoabdominal imaging (MRI, and/or CT and/or
somatostatin receptor imaging (PET or octreotide scan)) within 3 months prior to
inclusion or are due to undergo imaging within 3 months of inclusion to document the
presence of NETs,
- Regardless of the treatment they are receiving (treatment naïve or treated patient),
- Regardless of the type of disease associated with MEN1 (presence or absence of NET,
adenoma....),
- Patients who did not object to taking part in the study.
- Patients with proven MEN1, symptomatic or not, confirmed on the basis of the
following international criteria (Thakker et al.):
- patients with an MEN1 mutation;
- patients belonging to an identified MEN1 family in which at least one first-degree
relative has been affected and has at least one MEN1-related lesion;
- patients without a positive genetic test or a family history of the disease, but
with at least two of the three main MEN1 lesions (parathyroid adenomas,
duodenopancreatic NETs and pituitary tumours).
- Majors patients,
- Patients who have undergone thoracoabdominal imaging (MRI, and/or CT and/or
somatostatin receptor imaging (PET or octreotide scan)) within 3 months prior to
inclusion or are due to undergo imaging within 3 months of inclusion to document the
presence of NETs,
- Regardless of the treatment they are receiving (treatment naïve or treated patient),
- Regardless of the type of disease associated with MEN1 (presence or absence of NET,
adenoma....),
- Patients who did not object to taking part in the study.
- Person not affiliated to national health insurance
- Person subject to a measure legal protection (curatorship, guardianship, family
empowerment) or a court order
- Pregnant, parturient or breastfeeding mothers