ctDNA for Prediction of Relapse in Gastric Cancer

• Conditions: Stomach Neoplasms

• Registration Number: NCT02887612
• Lead Sponsor: Sun Yat-sen University

Brief Summary

Gastric cancer is one of the common malignant tumors in China, with relatively high incident rate and mortality among the population. Surgery is the conventional treatment option for early and intermediate-stage stage gastric cancer, but postoperative relapse is the major issue. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 166 bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation.ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it is considered as a new biomarker for tumor, which can be qualitative, quantitative and used for disease monitoring. The present clinical trial aims to elucidate the correlation between the serum ctDNA status and the prognosis of patients with early and intermediate-stage gastric cancer upon surgical treatment, and explore the possibility of clinical utility of serum ctDNA as a clinical index to predict postoperative relapse.

Detailed Description

Gastric cancer is one of the common malignant tumors in China, withrelatively high incident rate and mortality among the population. 95% of the gastric cancer is adenocarcinoma. 70% of the patients at the early stage show no obvious symptom, and only small number of them has nausea, vomiting, or symptoms that are similar to the of peptic ulcer disease.

Surgery is the conventional treatment option for early and middle stage gastric cancer, but postoperative relapse is the major issue. Currently, the only proven effective chemotherapies for gastric cancer are the taxane and platinum-based combination therapies. Also due to its molecular heterogeneity, the prognosis of gastric caner is highly varied among the patients. Therefore,there are not many effective targeting therapies available for the treatment of gastric cancer; and currently, trastuzumab and apatinib are the only two targeting drugs that have been clinically approved by CFDA.

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 166 bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation (2, 3). Although the mechanisms of its release have not been fully addressed, most reports considered apoptosis and/or necrosis of tumor cells as its main sources, which makes it a genomic reservoir of different tumor clones (4). Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome(5). Hence, it is considered as a new biomarker for tumor, which can be qualitative, quantitative and used for disease monitoring.

By monitoring the serum ctDNA mutational profile using Next Generation Sequencing (NGS), the present clinical trial aims to elucidate the correlation between the serum ctDNA status and the prognosis of patients with early and intermediate-stage gastric cancer upon surgical treatment, and explore the possibility of clinical utility of serum ctDNA as a clinical index to predict postoperative relapse. Moreover, by comparing the molecular profiles of patients with different prognosis, we may also screen out the molecular markers related to the prognosis of gastric cancer.

Study Timeline

• Study First Submitted: 2016-05-14
• Study First Submitted QC: 2016-08-29
• Study Start: 2016-09
• Study First Posted: 2016-09-02
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-25
• Last Update Posted: 2019-02-26
• Primary Completion: 2019-12
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Male or female ≥ 18 years of age at first visit.
2. Patients must have histologically confirmed early or intermediate-stage gastric cancer.
3. Patients need to have surgical treatment.
4. Patients must be able to provide sufficient fresh tissue/biopsies or minimum 5-10 FFPE sections for NGS analysis.
5. Patients must be able to follow the study visit schedule and willing to provide peripheral blood samples at the indicated time point.
6. Written informed consent must be obtained from patient or patient's legal representative and ability for patient to comply with the requirements of the study.

Exclusion Criteria

1. Patients who cannot provide peripheral blood samples prior to the surgical treatment will be excluded.
2. Patients with severe infection will be excluded.
3. Patients with other serious disease besides early or intermediate-stage gastric cancer will be excluded.
4. Pregnant women will be excluded.
5. Patients who are alcoholic or drug abusers will be excluded.
6. Patients with a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data will be excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Positive Predictive Value	through study completion, an average of 2 years	the proportions of patients with positive serum ctDNA (in any follow-up) that have postoperative relapse

Secondary Outcome Measures

Name	Time	Method
prognostic molecular markers	through study completion, an average of 2 years	to screen out the molecular markers related to the prognosis of gastric cancer by comparing the molecular profiles of patients with different prognosis

Trial Locations

Locations (1)

Medical Oncology,Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China