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

Gastric Cancer Clinical Trial

Official title:

Liquid Biopsy in Monitoring the Neoadjuvant Chemotherapy and Operation in Patients With Resectable or Locally Advanced Gastric or Gastro-oesophageal Junction Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03957564
• Other study ID #: AHQU-2019002
• Status: Recruiting
• Phase: Phase 2
• Start date: May 28, 2019
• Est. completion date: May 20, 2024

Study information

• Verified date: January 2020
• Source: Affiliated Hospital of Qinghai University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 20, 2024
• Est. primary completion date: May 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients with resectable or locally advanced gastric or gastro-oesophageal junction cancer(>T1 and N+) without distant metastases (M0).

2. Pathological examination confirmed gastric or gastro-oesophageal junction cancer (adenocarcinoma, signet ring cell carcinoma, mucinous adenocarcinoma, squamous cell carcinoma, regardless of the degree of tissue differentiation).

3. Ambulatory males or females, age = 18 years.

4. Karnofsky Performance Score (KPS) =70 or ECOG(Eastern Cooperative Oncology Group) performance status: 0 or 1.

5. Patients who can tolerate PSOX neoadjuvant chemotherapy.

6. Planning to undergo radical gastrectomy after neoadjuvant chemotherapy.

7. With cancer lesions that can be measured according to RECIST 1.1 criteria.

8. No prior antitumor treatment is allowed, including chemotherapy, radiotherapy, immune therapy or target therapy.

9. Adequate organ function as defined below: Hemoglobin = 9 g/dl, Absolute neutrophil count(ANC) = 1.5×109/L, Platelets = 100*109/L, Alkaline phosphatase( ALP) = 2.5×ULN,Total bilirubin(TBIL)= 1.5×ULN(upper limit of normal), Renal Serum Creatinine < 1.5 ULN, Serum Albumin = 30g/l.

Exclusion criteria:

1. Female in pregnancy or lactation, or refuse to receive contraception measures during chemotherapy.

2. With distant metastasis or peritoneal dissemination diagnosed by CT/EUS(endoscopic ultrasonography).

3. Underwent prior antitumor treatment, including chemotherapy, radiotherapy, immune therapy or target therapy.

4. Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease or condition that would make the subject inappropriate for study participation.

5. Clinically serious cardiac disease or pulmonary dysfunction.

6. Refuse to provide blood/tissue sample.

7. Other situation to be judged not adaptive to the study by investigators.

Related Conditions & MeSH terms

• Gastric Cancer
• Gastro-oesophageal Junction Cancer
• Stomach Neoplasms

Intervention

Drug:
• Neoadjuvant chemotherapy with PSOX regimen.
Resectable gastric or gastro-oesophageal junction cancer patients receiving neoadjuvant chemotherapy with PSOX(Paclitaxel+Oxaliplatin+S1)regimen. The details are as follows: Paclitaxel 135mg/m2 d1, Oxaliplatin 85mg/m2 d1, S1 40-60mg/m2 twice daily, d1-14 , 21 days is one cycle.

Other:
• Detect the imaging data and levels of CTC, ctDNA, cfDNA, CEA, CA19-9, CA72-4 in plasma.
Detect the imaging data and levels of CTC, ctDNA, cfDNA, CEA, CA19-9, CA72-4 in 3 time points:Before neoadjuvant chemotherapy, After 2-3 cycles of neoadjuvant chemotherapy, 10 days after operation.
• Detect the tumor related DNA in pathological tissues after operation.
Detect the tumor related DNA in pathological tissues after operation.
• Follow-up of DFS and OS in patients with gastric cancer after operation.
Follow-up of DFS and OS in patients with locally advanced or resectable gastric or gastro-oesophageal Junction cancer.

Locations

Country	Name	City	State
China	Jiuda Zhao	Xining	Qinghai

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital of Qinghai University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of CTC pre- and post- neoadjuvant chemotherapy and after operation.	Numbers of CTC pre- and post- neoadjuvant chemotherapy and after operation.	2 years
Primary	Types of CTC pre- and post- neoadjuvant chemotherapy and after operation.	Types of CTC pre- and post- neoadjuvant chemotherapy and after operation.	2 years
Primary	Mutation rate of ctDNA pre- and post- neoadjuvant chemotherapy and after operation.	Mutation rate of ctDNA pre- and post- neoadjuvant chemotherapy and after operation.	2 years
Primary	Concentration of cfDNA pre- and post- neoadjuvant chemotherapy and after operation.	Concentration of cfDNA pre- and post- neoadjuvant chemotherapy and after operation.	2 years
Primary	The relationship between tumor response and changes in numbers of CTC 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
Primary	The relationship between tumor response and mutation of ctDNA 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
Secondary	Disease Free Survival(DFS)	The relationship between CTC, ctDNA and cfDNA and DFS in patients with resectable or locally advanced gastric or gastro-oesophageal junction cancer.	2 years
Secondary	Overall survival(OS)	The relationship between CTC, ctDNA and cfDNA and OS in patients with resectable or locally advanced gastric or gastro-oesophageal junction cancer.	2 years
Secondary	Types of tumor-associated DNA in tumor tissues after operation.	Types of tumor-associated DNA in tumor tissues after operation.	2 years