Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Evaluating Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

This study is designed to evaluate the potential clinical utility of ctDNA in the field of gastric cancer treatment,especially the usage of an indicator of MRD(minimal residual disease) in post radical gastrectomy patients. The primary purpose of this trial is to demonstrate if the postoperative ctDNA analysis could be used as an indicator of MRD or adjuvant chemotherapy response in advanced gastric cancer after radical gastrectomy.The second purpose is to describe the profile of ctDNA in gastric cancer.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Combination product: AVENIO ctDNA surveillance kit

Detailed Description

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer related death worldwide.Incidence shows clear regional and sex variations-rates are highest in Eastern Asia, Eastern Europe, and South America and lowest in Northern and Southern Africa. In China, gastric cancer accounts for nearly 16% of all malignant tumors and more than 80% of gastric cancer are in advanced stage.

Minimal residual disease (MRD) was proposed to describe the remaining tumor cells after treatment with curative intent. For curable gastric cancer, MRD means residential cancer cells after radical gastrectomy which share phenotypic similarity and genetic heritage with the original tumor. Treating MRD can increase the rates of cure had been supported by the experience of using adjuvant therapy for some type of solid tumor (for example, colorectal cancer, breast cancer). The challenge in monitoring the MRD in gastric cancer patients is that there is no very sensitive method. Computed tomography(CT) and blood tumor markers are either difficult to detect peritonial dissemination, the most frequent recurrent pattern in gastric caner or with limited sensitivity and specificity.

Tumor-specific DNA mutations detected in the cell-free component of peripheral blood, which is known as circulating tumor DNA (ctDNA), in most patients, allow for the noninvasive molecular characterization detection of tumors, including genetic changes that are revealed by the selective pressure of adjuvant therapies. Considering the origin of ctDNA, it can be from different subclones of primary tumor or both primary and metastatic tumors, the ctDNA may overcome the problems caused by tumor heterogeneity. Additionally, the short half-life of ctDNA, about 2 hours, makes ctDNA an ideal dynamic marker of tumor bulk.

In summary, the ctDNA is a good candidate to be a new kind of blood tumor marker. The preliminary studies had shown very good prospects in some tumors, including breast caner and colon cancer.But little was known in gastric cancer, so we designed this study to demonstrate the potential clinical utility of ctDNA in the field of gastric cancer treatment, especially the usage of an indicator of MRD in post radical gastrectomy patients.

• Study Type: Observational
• Enrollment (Anticipated): 55

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Zhongshan Hospital Fudan University
      • Contact: Zhaoqing Tang, MD; Email: tang.zhaoqing@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Stomach adenocarcinoma patients who plan to receive radical gastrectomy and continuous circulating tumor DNA monitoring

Description

Inclusion Criteria:

1. Male or female patients age 18 - 75.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
3. Histologically proven primary stomach adenocarcinoma with Lauren type by gastroscopic biopsy before operation.
4. Clinical stage is cT3/4N+M0 and the tumor is resectable in initial evaluation.
5. No preoperative tumor therapy, including chemotherapy, radiotherapy, et al.
6. No concomitant other malignant tumor or treated malignant tumor within last five years.
7. Signed informed consent.
8. Consent to provide research blood/tissue samples and clinicopathological information.

Exclusion Criteria:

1. Radical gastrectomy was found cannot be achieved during operation due to metastasis or adjacent organ invasion.
2. Only preoperative or postoperative blood sample was harvest or qualified.
3. No qualified paired tissue samples.
4. No complete clinicopatholoical information and follow-up.
5. Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ctDNA detection; The blood samples for ctDNA and other tumor markers (such as CEA, et al.) will be first collected within 7 days before surgery, and then be tested after radical gastrectomy in scheduled interval.	Combination product: AVENIO ctDNA surveillance kit; AVENIO circulating tumor DNA (ctDNA) Analysis Kits is a portfolio of three next-generation sequencing (NGS) liquid biopsy assay kits for oncology research: the AVENIO ctDNA Targeted Kit, Expanded Kit and Surveillance Kit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of disease recurrence risk according to first positive ctDNA detection	Time is measured from first positive ctDNA detection to disease-free survival event.	2 years
Description of ctDNA changing to adjuvant chemotherapy response	For subjects with postoperative positive ctDNA, time is measured from first adjuvant chemotherapy to first negative ctDNA detection.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leading time between ctDNA detection and disease recurrence detected by conventional methods	Time is measured between first positive ctDNA detection and first recurrence detected by conventional methods.	2 years
The ctDNA level/mutations in gastric cancer preoperatively	Profiling of the most frequently detected gene mutations and level of mutations in preoperative ctDNA.	Within 7 days before operation

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Zhaoqing Tang, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): May 31, 2021

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): June 27, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Gastric Cancer; Circulating Tumor DNA; Minimal Residue Disease; Chemotherapy Response
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: ZSGC-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No