LIQUID: Peritoneal Lavage Liquid Biopsy in Patients With Gastric Cancer

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Other)

Overall Status

Recruiting

CT.gov ID

NCT04943406

Collaborator

(none)

150

Enrollment

Location

59.8

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study investigates the prognostic role of liquid biopsy in patients with locally advanced gastric cancer.

Liquid biopsy for the detection of circulating tumor DNA will be performed:

In the peritoneal lavage, during staging laparoscopy (if indicated) and during curative gastrectomy
In plasma, before staging laparoscopy (if indicated), before curative gastrectomy, at hospital discharge, three months after surgery/at the end of adjuvant therapy, and in case of disease recurrence.

The aim of this study is to determine the predictive power of liquid biopsy on overall survival and disease free survival.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Gastric Adenocarcinoma

Detailed Description

The purpose of this prospective observational study is to determine the prognostic role of liquid biopsy for the detection of circulating tumor DNA (ctDNA) in patients with locally advanced gastric cancer.

Patients with cT3-4 and or N+ gastric cancer will proceed to either staging laparoscopy, if preoperative chemotherapy is indicated, or upfront radical surgery within 2 weeks from the last imaging assessment.

Liquid biopsy will be performed with peritoneal lavage and blood samples. Peritoneal lavage is performed with 500 ml of saline, starting from the retrogastric space (100 ml) and following clockwise from right upper quadrant to right lower using 100 ml for each quadrant. At the end of peritoneal lavage, 250 ml of saline solution is collected over the liver, after having positioned the patient in Trendelenburg position and on the right side. Of the collected fluid, 50 mL will be sent for cytological examination and 50 mL will be stocked for ctDNA analyses.

In case of upfront radical surgery, liquid biopsy will be performed at the following time points:

Through blood samples performed before skin incision and 7-10 days after radical surgery;
Through peritoneal lavage, immediately after laparotomy/laparoscopy.

In case of staging laparoscopy, liquid biopsy will be performed with blood samples, just before skin incision, and with peritoneal lavage. Patients with no evidence of peritoneal dissemination after staging laparoscopy will undergo induction chemotherapy according to the FLOT scheme or per investigators' judgment, and restaged after 4 cycles. Patients still fulfilling the inclusion criteria will undergo radical surgery within 3 weeks from the last chemotherapy cycle. Patients will then undergo liquid biopsy with the same scheme as for upfront radical surgery.

Patients who are clinically fit, and for whom there is clinical indication, will undergo adjuvant chemotherapy. Blood samples for ctDNA will be collected at the end of the last cycle of adjuvant chemotherapy, or at the end of the third postoperative month for those patients not undergoing postoperative chemotherapy. Then, patients will be followed up according to standard protocols by means of CT scan, CEA assessment and clinical visit every six months for the first three years after surgery and then yearly up to five years after local treatments. Blood samples for ctDNA will be collected at detection of cancer recurrence.

Study Design

Study Type:

Observational

Anticipated Enrollment :

150 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Prognostic Performance of Liquid Biopsy in Peritoneal Lavage and Plasma of Patients With Locally Advanced Gastric Cancer (LIQUID Study)

Actual Study Start Date :

May 8, 2020

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Outcome Measures

Primary Outcome Measures

Prognostic impact of ctDNA positivity [At disease recurrence or at 3-year follow up]
To evaluate the prognostic impact (overall survival and disease-free survival) of ctDNA positivity in peritoneal lavage and peripheral blood of patients with resectable, stage < IV, gastric cancer

Secondary Outcome Measures

Rate of ctDNA positivity in peritoneal lavage and peripheral blood [Peritoneal lavage: at staging laparoscopy and at curative surgery; plasma: before staging laparoscopy, before curative surgery, at hospital discharge, 3 months after surgery/at the end of adjuvant therapy, at disease recurrence]
To evaluate the rate of ctDNA positivity in peritoneal lavage and peripheral blood of patients with resectable, stage < IV, gastric cancer
Correlation between ctDNA detection and clinical and tumoral patients' characteristics [Peritoneal lavage: at staging laparoscopy and at curative surgery; plasma: before staging laparoscopy, before curative surgery, at hospital discharge, 3 months after surgery/at the end of adjuvant therapy, at disease recurrence]
To evaluate the correlation between ctDNA detection and variables related to the clinical and histopathological characteristics of each patient
Dynamics of ctDNA detection in peritoneal lavage and peripheral blood in patients undergoing pre-operative chemotherapy [Peritoneal lavage: at staging laparoscopy and at curative surgery; plasma: before staging laparoscopy, before curative surgery, at hospital discharge, 3 months after surgery/at the end of adjuvant therapy, at disease recurrence]
To evaluate the dynamics of ctDNA detection in peritoneal lavage and peripheral blood in patients undergoing pre-operative chemotherapy at different time points
Dynamics of ctDNA detection in peripheral blood in patients undergoing pre-and post-operative chemotherapy, and at disease recurrence [Peritoneal lavage: at staging laparoscopy and at curative surgery; plasma: before staging laparoscopy, before curative surgery, at hospital discharge, 3 months after surgery/at the end of adjuvant therapy, at disease recurrence]
To evaluate the dynamics of ctDNA detection in peripheral blood in patients undergoing pre-and post-operative chemotherapy, and at disease recurrence at different time points
Prognostic impact of ctDNA positivity in peritoneal lavage and peripheral blood on the risk of peritoneal and distant metastases [Peritoneal lavage: at staging laparoscopy and at curative surgery; plasma: before staging laparoscopy, before curative surgery, at hospital discharge, 3 months after surgery/at the end of adjuvant therapy, at disease recurrence]
To evaluate the correlation between ctDNA positivity in peritoneal lavage and peripheral blood and the risk of developing peritoneal and distant metastases

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically proven gastric or gastro-esophageal junction (GEJ -Siewert type II -III) adenocarcinoma
More than cT2 and/or N + (UICC 8th edition)
Written informed consent

Exclusion Criteria:

Presence of ascites or distant metastases
Previous chemotherapy for gastric adenocarcinoma
Previous gastric surgery
Absolute contraindications to surgery
Concomitant malignancies or history of other malignancies in the previous 5 years (with exception of in situ cervical carcinoma, basal cell carcinoma, superficial bladder tumors are allowed if curatively treated).