ctDNA for Prediction of Relapse in Gastric Cancer

Stomach Neoplasms Clinical Trial

Official title:

A Prospective Study of Blood Circulating Tumor DNA for the Prediction of Postoperative Relapse in Early and Intermediate-Stage Gastric Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02887612
• Other study ID #: ctDNA001
• Status: Recruiting
• Start date: September 2016
• Est. completion date: June 2020

Study information

• Verified date: February 2019
• Source: Sun Yat-sen University
• Contact: Feng Wang, MD.,PhD.
• Phone: 86-2087343804
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Stomach Neoplasms

Intervention

Other:
• ctDNA test

Locations

Country	Name	City	State
China	Medical Oncology,Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (4)

Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001 Feb 15;61(4):1659-65. — View Citation

Jiang P, Chan CW, Chan KC, Cheng SH, Wong J, Wong VW, Wong GL, Chan SL, Mok TS, Chan HL, Lai PB, Chiu RW, Lo YM. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1317-25. doi: 10.1073/pnas.1500076112. Epub 2015 Feb 2. — View Citation

Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta. 2001 Nov;313(1-2):139-42. — View Citation

Yu SC, Lee SW, Jiang P, Leung TY, Chan KC, Chiu RW, Lo YM. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013 Aug;59(8):1228-37. doi: 10.1373/clinchem.2013.203679. Epub 2013 Apr 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive Predictive Value	the proportions of patients with positive serum ctDNA (in any follow-up) that have postoperative relapse	through study completion, an average of 2 years
Secondary	prognostic molecular markers	to screen out the molecular markers related to the prognosis of gastric cancer by comparing the molecular profiles of patients with different prognosis	through study completion, an average of 2 years