- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07574957
Prediction of Peritoneal Dissemination of Digestive Tumors Through the Study of Circulating Tumor DNA (PREDIPER)
Prédiction de la dissémination péritonéale Des Tumeurs Digestives Par étude de l'ADN Tumoral Circulant
The peritoneum is a relatively frequent metastatic site in digestive tumors (colon, stomach, pancreas) and is characterized by a poorer prognosis compared with other metastatic sites such as the lung or liver. Its dissemination pathway is complex and most often involves crossing the hemato-peritoneal barrier. This type of metastasis is difficult to visualize on imaging at an early stage, and surgical exploration may be required. In gastric cancer in particular, exploratory laparoscopy is part of the initial staging work-up for locally advanced tumors to assess the presence or absence of peritoneal metastases. It is therefore important to develop new, less invasive detection or prediction methods.
Circulating tumor DNA (ctDNA) is a promising non-invasive blood biomarker that can assist clinicians as a prognostic/predictive biomarker and/or a tool for monitoring response to anti-tumor therapies. This marker is most often assessed in plasma, but recent data suggest that tumor DNA may also be detected in other biological fluids such as peritoneal fluid. A preliminary study conducted by our team showed the ability to detect tumor DNA in peritoneal fluid from patients with peritoneal carcinomatosis of various origins, with a sensitivity of 75%. In gastric cancer, a recent meta-analysis demonstrated an increased risk of peritoneal metastases when peritoneal tumor DNA was positive (RR 13.81 [95% CI, 8.11-23.53]), as well as a reduction in 3-year recurrence-free survival (RR 5.37 [95% CI, 1.39-20.74]) and overall survival (HR 4.13 [95% CI, 1.51-11.32]).
The objective of this cohort is to evaluate the prognostic impact of circulating tumor DNA (ctDNA) in plasma and/or peritoneal fluid on the risk of developing peritoneal metastases. The primary endpoint is: Peritoneal recurrence rate according to tumor DNA positivity status (positive vs negative).
Přehled studie
Postavení
Detailní popis
After screening, verification of inclusion and exclusion criteria, information and consent, patients will be enrolled in the study.
Several samples will be collected at different time points during patient management, in addition to samples already performed as part of routine care. No intervention or sampling will occur at a time point specifically required for research purposes. Blood and peritoneal fluid samples will always be collected concomitantly. They will then be transported to the molecular biology laboratory for initial DNA extraction. After extraction, samples will be stored at -80 °C until analysis.
The treatments offered to the patient follow standard-of-care recommendations and are not modified by participation in the study.
Three independent cohorts will be evaluated: gastric cancer, colon cancer, and pancreatic cancer.Depending on the type of cancer and the therapeutic strategy, different samples will be collected.
Systematic sampling:
Plasma: at diagnosis, at the time of surgery, in the early postoperative period, and 1 month after surgery (during the postoperative visit).
Peritoneal fluid: at the time of surgery and in the early postoperative period.
Specific sampling:
Peritoneal fluid: during pre-therapeutic exploratory laparoscopy (gastric cancer) or during diverting colostomy (obstructive colon cancer).
In total:
Gastric cancer: 3 peritoneal fluid samples and 4 blood samples.
Colon cancer: 2 peritoneal fluid samples and 3 blood samples systematically, plus 1 optional blood and peritoneal fluid sample (only in case of diverting colostomy).
Pancreatic cancer: 2 peritoneal fluid samples and 3 systematic blood samples, plus 1 optional blood sample (in case of neoadjuvant treatment).
Blood sampling:
2 EDTA tubes (molecular biology)
Peritoneal fluid sampling:
2 dry tubes (molecular biology, pathology)
For intraoperative sampling, a peritoneal washing is performed with 200 mL of 0.9% NaCl instilled into the abdominal cavity; then 50 mL are collected from the pouch of Douglas.
For the postoperative period, the sample will be collected between postoperative day 2 and day 5 directly from the drainage fluid (collected from the drain reservoir left in place at the end of surgery).
ctDNA analysis: NGS (next-generation sequencing), or high-throughput sequencing, is a molecular biology method that enables the rapid sequencing of millions of DNA molecules simultaneously and is used to identify point mutations as well as insertions, duplications, and deletions. It will be used for both plasma analysis and peritoneal fluid analysis.
Typ studie
Zápis (Odhadovaný)
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Metoda odběru vzorků
Studijní populace
Popis
Inclusion Criteria:
- Age > 18 years
- Signed non-opposition form
- For gastric cancer: histologically confirmed gastric adenocarcinoma >T2 and/or N+; for colon cancer: histologically confirmed colonic adenocarcinoma >T2; for pancreatic cancer: histologically confirmed pancreatic adenocarcinoma >T2
- No metastases on the initial staging work-up
- No contraindication to curative-intent surgical treatment
Exclusion Criteria:
- Primary tumor metastatic at diagnosis
- Presence of ascites or distant metastases
- Synchronous cancer or prior history of cancer within the past 5 years
- Contraindication to curative surgical treatment
- Any patient unable to comply with the study's medical follow-up for geographic, social, or psychological reasons
- Patients under legal guardianship/protection, or unable to read, understand, and sign the information notice and consent form
- Patients not affiliated with the social security system
Studijní plán
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
|---|
|
localized gastric cancer
resectable tumor receiving neoajuvant chemotherapy and curative gastrectomy
|
|
localized colorectal cancer
resectable tumor receiving neoajuvant chemotherapy or not and curative colectomy
|
|
localized pancreatic cancer
resectable tumor receiving neoajuvant chemotherapy or not and curative pancreatectomy
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
peritoneal progression free survival (PPFS)
Časové okno: Time from the start of treatment until peritoneal recurrence assessed up to 36 months
|
PPFS will be evaluated according to the circulating tumor DNA in the blood and in the peritoneal fluid
|
Time from the start of treatment until peritoneal recurrence assessed up to 36 months
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
disease free survival (DFS)
Časové okno: Time from the start of treatment until recurrence assessed up to 36 months
|
DFS will be evaluated according to the circulating tumor DNA in the blood and in the peritoneal fluid
|
Time from the start of treatment until recurrence assessed up to 36 months
|
Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Onemocnění endokrinního systému
- Novotvary podle místa
- Novotvary
- Střevní nemoci
- Gastrointestinální novotvary
- Novotvary trávicího systému
- Nemoci trávicího systému
- Gastrointestinální onemocnění
- Onemocnění žaludku
- Střevní novotvary
- Rektální onemocnění
- Novotvary endokrinních žláz
- Onemocnění slinivky břišní
- Onemocnění tlustého střeva
- Novotvary žaludku
- Kolorektální novotvary
- Novotvary pankreatu
Další identifikační čísla studie
- APHP251031
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Studuje produkt zařízení regulovaný americkým úřadem FDA
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