Liquid Biopsy in Monitoring the Neoadjuvant Chemotherapy and Operation in Gastric Cancer

Phase 2

• Conditions: Gastric Cancer; Gastro-oesophageal Junction Cancer
• Interventions: Drug: Neoadjuvant chemotherapy with PSOX regimen.; Other: Detect the imaging data and levels of CTC, ctDNA, cfDNA, CEA, CA19-9, CA72-4 in plasma.; Other: Detect the tumor related DNA in pathological tissues after operation.; Other: Follow-up of DFS and OS in patients with gastric cancer after operation.

• Registration Number: NCT03957564
• Lead Sponsor: Affiliated Hospital of Qinghai University

Brief Summary

To explore the clinical value of dynamic detection of circulating tumor cells(CTCs), circulating tumor DNA(ctDNA) and cell-free DNA(cfDNA) in neoadjuvant chemotherapy and operation of resectable or locally advanced gastric or gastro-oesophageal junction cancer.

Detailed Description

Gastric cancer(GC) is one of the common malignant tumors in world, with relatively high incident rate and mortality among the population. Neoadjuvant chemotherapy is often needed before operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. Neoadjuvant chemotherapy should be combined with platinum and fluorouracil, or paclitaxel should be added on the basis of platinum and fluorouracil. The efficacy of neoadjuvant chemotherapy for GC patients is usually evaluated by computer tomography(CT) scans with RECIST 1.1 criteria and the blood level of carcinoembryonic antigen(CEA),CA19-9 (carbohydrate antigen 19-9)and CA72-4(carbohydrate antigen 72-4) tumor markers.

CTC originating from solid tumors are related to hematogenous metastatic spread to distant sites. Therefore, CTC analysis has clinical relevance as a biomarker to noninvasively monitor cancer progression and guide therapy.Moreover, ctDNA is a part of cfDNA derived from apoptotic, necrotic or secreted DNA fragments of tumor cells, ctDNA contains the same genetic defects as the tumor DNA of its origin, such as point mutation and rearrangement. We speculate CTC, ctDNA and cfDNA are new biomarkers for tumor, which can guide neoadjuvant chemotherapy and surgical treatment for patients with locally advanced or resectable gastric or gastro-oesophageal junction cancer.

In this study, investigators will compare the clinical value of the dynamic detection of CTC, ctDNA and cfDNA with CEA ,CA19-9 and CA72-4 tumor markers and CT scan according the RECIST 1.1 criteria in neoadjuvant chemotherapy and operation for resectable or locally advanced gastric or gastro-oesophageal junction cancer. Investigators will also explore the relationship between the dynamic changes of CTC, ctDNA and cfDNA and the prognosis of patients after operation. The results will provide lots of meaningful information which may further improve the treatment of locally advanced or resectable gastric or gastro-oesophageal junction cancer.

Study Timeline

• Study First Submitted: 2019-05-07
• Study First Submitted QC: 2019-05-17
• Study First Posted: 2019-05-21
• Study Start: 2019-05-28
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-18
• Last Update Posted: 2020-01-22
• Primary Completion: 2022-05-20
• Study Completion: 2024-05-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients receiving neoadjuvant chemotherapy.	Detect the imaging data and levels of CTC, ctDNA, cfDNA, CEA, CA19-9, CA72-4 in plasma.	1. Compare the monitoring of CTC, ctDNA and cfDNA with the results of CT scan and the blood level of CEA ,CA19-9 and CA72-4 tumor markers to explore the clinical value of dynamic detection of CTC, ctDNA and cfDNA in neoadjuvant chemotherapy and operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. 2. Explore the clinical value of different types of CTC in neoadjuvant chemotherapy and Operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. CTC can be classified into three types: epithelial CTC, mesenchymal CTC, hybrids CTC. 3. Explore the consistency between plasma ctDNA and tumor related DNA in pathological tissues after operation. 4. To explore the relationship between the dynamic changes of plasma CTC, ctDNA and cfDNA levels and the prognosis of patients after operation.
Patients receiving neoadjuvant chemotherapy.	Neoadjuvant chemotherapy with PSOX regimen.	1. Compare the monitoring of CTC, ctDNA and cfDNA with the results of CT scan and the blood level of CEA ,CA19-9 and CA72-4 tumor markers to explore the clinical value of dynamic detection of CTC, ctDNA and cfDNA in neoadjuvant chemotherapy and operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. 2. Explore the clinical value of different types of CTC in neoadjuvant chemotherapy and Operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. CTC can be classified into three types: epithelial CTC, mesenchymal CTC, hybrids CTC. 3. Explore the consistency between plasma ctDNA and tumor related DNA in pathological tissues after operation. 4. To explore the relationship between the dynamic changes of plasma CTC, ctDNA and cfDNA levels and the prognosis of patients after operation.
Patients receiving neoadjuvant chemotherapy.	Detect the tumor related DNA in pathological tissues after operation.	1. Compare the monitoring of CTC, ctDNA and cfDNA with the results of CT scan and the blood level of CEA ,CA19-9 and CA72-4 tumor markers to explore the clinical value of dynamic detection of CTC, ctDNA and cfDNA in neoadjuvant chemotherapy and operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. 2. Explore the clinical value of different types of CTC in neoadjuvant chemotherapy and Operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. CTC can be classified into three types: epithelial CTC, mesenchymal CTC, hybrids CTC. 3. Explore the consistency between plasma ctDNA and tumor related DNA in pathological tissues after operation. 4. To explore the relationship between the dynamic changes of plasma CTC, ctDNA and cfDNA levels and the prognosis of patients after operation.
Patients receiving neoadjuvant chemotherapy.	Follow-up of DFS and OS in patients with gastric cancer after operation.	1. Compare the monitoring of CTC, ctDNA and cfDNA with the results of CT scan and the blood level of CEA ,CA19-9 and CA72-4 tumor markers to explore the clinical value of dynamic detection of CTC, ctDNA and cfDNA in neoadjuvant chemotherapy and operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. 2. Explore the clinical value of different types of CTC in neoadjuvant chemotherapy and Operation for locally advanced or resectable gastric or gastro-oesophageal junction cancer. CTC can be classified into three types: epithelial CTC, mesenchymal CTC, hybrids CTC. 3. Explore the consistency between plasma ctDNA and tumor related DNA in pathological tissues after operation. 4. To explore the relationship between the dynamic changes of plasma CTC, ctDNA and cfDNA levels and the prognosis of patients after operation.

Primary Outcome Measures

Name	Time	Method
Numbers of CTC pre- and post- neoadjuvant chemotherapy and after operation.	2 years	Numbers of CTC pre- and post- neoadjuvant chemotherapy and after operation.
Types of CTC pre- and post- neoadjuvant chemotherapy and after operation.	2 years	Types of CTC pre- and post- neoadjuvant chemotherapy and after operation.
Mutation rate of ctDNA pre- and post- neoadjuvant chemotherapy and after operation.	2 years	Mutation rate of ctDNA pre- and post- neoadjuvant chemotherapy and after operation.
Concentration of cfDNA pre- and post- neoadjuvant chemotherapy and after operation.	2 years	Concentration of cfDNA pre- and post- neoadjuvant chemotherapy and after operation.
The relationship between tumor response and mutation of ctDNA pre- and post-neoadjuvant chemotherapy and after operation.	2 years	The relationship between tumor response and mutation of ctDNA pre- and post-neoadjuvant chemotherapy and after operation.
The relationship between tumor response and changes in numbers of CTC pre- and post-neoadjuvant chemotherapy and after operation.	2 years	The relationship between tumor response and changes in numbers of CTC pre- and post-neoadjuvant chemotherapy and after operation.

Secondary Outcome Measures

Name	Time	Method
Disease Free Survival(DFS)	2 years	The relationship between CTC, ctDNA and cfDNA and DFS in patients with resectable or locally advanced gastric or gastro-oesophageal junction cancer.
Overall survival(OS)	2 years	The relationship between CTC, ctDNA and cfDNA and OS in patients with resectable or locally advanced gastric or gastro-oesophageal junction cancer.
Types of tumor-associated DNA in tumor tissues after operation.	2 years	Types of tumor-associated DNA in tumor tissues after operation.

Trial Locations

Locations (1)

Jiuda Zhao; 🇨🇳 Xining, Qinghai, China