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

January 18, 2020 updated by: Jiuda Zhao, Affiliated Hospital of Qinghai University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Qinghai
      • Xining, Qinghai, China, 810000
        • Recruiting
        • Jiuda Zhao
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Patients receiving neoadjuvant chemotherapy.
  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.
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.
Other: Detect the tumor related DNA in pathological tissues after operation.
Detect the tumor related DNA in pathological tissues after operation.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numbers of CTC pre- and post- neoadjuvant chemotherapy and after operation.
Time Frame: 2 years
Numbers of CTC pre- and post- neoadjuvant chemotherapy and after operation.
2 years
Types of CTC pre- and post- neoadjuvant chemotherapy and after operation.
Time Frame: 2 years
Types of CTC pre- and post- neoadjuvant chemotherapy and after operation.
2 years
Mutation rate of ctDNA pre- and post- neoadjuvant chemotherapy and after operation.
Time Frame: 2 years
Mutation rate of ctDNA pre- and post- neoadjuvant chemotherapy and after operation.
2 years
Concentration of cfDNA pre- and post- neoadjuvant chemotherapy and after operation.
Time Frame: 2 years
Concentration of cfDNA 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.
Time Frame: 2 years
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 mutation of ctDNA pre- and post-neoadjuvant chemotherapy and after operation.
Time Frame: 2 years
The relationship between tumor response and mutation of ctDNA pre- and post-neoadjuvant chemotherapy and after operation.
2 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affiliated Hospital of Qinghai University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 28, 2019

Primary Completion (ANTICIPATED)

May 20, 2022

Study Completion (ANTICIPATED)

May 20, 2024

Study Registration Dates

First Submitted

May 7, 2019

First Submitted That Met QC Criteria

May 17, 2019

First Posted (ACTUAL)

May 21, 2019

Study Record Updates

Last Update Posted (ACTUAL)

January 22, 2020

Last Update Submitted That Met QC Criteria

January 18, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AHQU-2019002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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