Dynamic Circulating Tumor DNA Monitoring to Guide Systemic Therapy in Gastric Cancer

A Prospective Phase II Study of Dynamic Circulating Tumor DNA to Predict and Guide Systemic Treatment in Patients With Gastric Cancer

This study aims to evaluate the clinical value of circulating tumor DNA (ctDNA) as a minimally invasive biomarker for monitoring treatment response and guiding systemic therapy in patients with gastric or gastroesophageal junction adenocarcinoma.

Gastric cancer is often diagnosed at an advanced stage and shows substantial biological heterogeneity. Current treatment decisions mainly rely on imaging and clinical assessment, which may not reflect early molecular changes or minimal residual disease. Circulating tumor DNA, released from tumor cells into the bloodstream, can provide real-time information on tumor burden and treatment response through simple blood sampling.

This is a prospective, open-label, phase II exploratory study conducted at a single center. Patients will be enrolled into three clinical cohorts according to their treatment stage: (1) neoadjuvant or conversion therapy cohort, (2) adjuvant therapy cohort after curative surgery, and (3) advanced or metastatic disease cohort receiving systemic therapy. Blood samples for ctDNA analysis will be collected before treatment and at predefined time points during treatment.

The study will assess whether changes in ctDNA levels, including ctDNA clearance or reduction, are associated with treatment response, recurrence risk, and survival outcomes. In selected validation phases, treatment strategies may be adjusted based on ctDNA results, while all treatments remain within standard guideline-recommended regimens.

The results of this study may help determine whether ctDNA can be used as a practical tool to improve treatment monitoring and support more personalized management of gastric cancer.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Diagnostic test: Circulating Tumor DNA (ctDNA) Analysis; Drug: Standard Systemic Therapy for Gastric Cancer

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weijian Guo; Phone Number: 02164175590; Email: guoweijian1@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Weijian Guo; Phone Number: 02164175590; Email: guoweijian1@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-

Age ≥18 years. Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma.

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Adequate organ function within 7 days prior to enrollment, including:

Absolute neutrophil count ≥1.5 × 10⁹/L Platelet count ≥80 × 10⁹/L Hemoglobin ≥80 g/L Total bilirubin ≤1.5 × upper limit of normal (ULN) AST and ALT ≤2.5 × ULN (≤5 × ULN in case of liver metastases) Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min Serum albumin ≥30 g/L Estimated life expectancy ≥3 months. Willingness to provide blood samples for circulating tumor DNA (ctDNA) analysis.

Signed written informed consent prior to any study-related procedures.

Cohort-Specific Inclusion Criteria:

Neoadjuvant/Conversion Cohort:

8. Planned to receive neoadjuvant or conversion systemic therapy followed by potential surgery.

9. Locally advanced (T3-T4a and/or N+, M0) or oligometastatic disease (≤1 metastatic organ and ≤5 lesions) considered potentially resectable after systemic therapy.

10. No prior systemic therapy for gastric cancer.

Adjuvant Cohort:

11. Completion of curative-intent surgery for gastric cancer. 12. Pathological stage II-III disease without distant metastasis. 13. Planned to receive standard adjuvant chemotherapy (e.g., XELOX or SOX).

Advanced Disease Cohort:

14. Unresectable or metastatic disease not amenable to curative surgery. 15. Planned to receive systemic therapy, including chemotherapy with or without immunotherapy, as first-line or later-line treatment.

16. At least one measurable lesion according to RECIST v1.1.

Exclusion Criteria:

-

History of another malignancy within 5 years, except for adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer.

Uncontrolled central nervous system metastases or primary brain tumors.

Severe or uncontrolled comorbidities, including but not limited to:

Unstable cardiovascular disease (e.g., recent myocardial infarction, unstable angina, congestive heart failure) Severe infection Active disseminated intravascular coagulation Significant bleeding tendency Significant organ dysfunction that, in the investigator's judgment, would compromise patient safety.

Symptomatic pleural effusion or ascites requiring intervention. Any condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ctDNA-Guided Standard Treatment Arm; Participants in this arm will receive guideline-recommended systemic treatment according to their disease stage, including neoadjuvant or conversion therapy, adjuvant chemotherapy, or systemic therapy for advanced disease. Plasma circulating tumor DNA (ctDNA) will be collected at predefined time points during treatment. Treatment decisions, including continuation or adjustment of therapy in selected phases, will be guided by predefined ctDNA molecular response criteria within standard-of-care options. No investigational drugs will be used.

Diagnostic test: Circulating Tumor DNA (ctDNA) Analysis; Plasma circulating tumor DNA (ctDNA) will be analyzed using a targeted next-generation sequencing panel to assess tumor-specific genetic alterations. Blood samples will be collected at predefined time points during treatment. ctDNA dynamics, including clearance or changes in mutation allele frequency, will be used to evaluate molecular response and guide treatment decisions within standard-of-care options.; Drug: Standard Systemic Therapy for Gastric Cancer; Participants will receive guideline-recommended systemic treatment according to disease stage and clinical practice, including neoadjuvant or conversion therapy, adjuvant chemotherapy, or systemic therapy for advanced disease. Treatment regimens may include fluoropyrimidine- and platinum-based chemotherapy, with or without PD-1 inhibitors or other standard agents. All treatments are administered according to standard-of-care and are not investigational.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by investigators.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-free survival (PFS) is defined as the time from study enrollment to the first documentation of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.	Up to 36 months
Overall Survival (OS)	Overall survival (OS) is defined as the time from study enrollment to death from any cause.	Up to 36 months
Disease Control Rate (DCR)	Disease control rate (DCR) is defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1.	Up to 24 months
Recurrence-Free Survival (RFS)	Recurrence-free survival (RFS) is defined as the time from study enrollment (or surgery for applicable patients) to the first documentation of disease recurrence.	Up to 36 months
Pathological Complete Response Rate (pCR)	Pathological complete response (pCR) is defined as the absence of residual tumor cells in the resected specimen after neoadjuvant or conversion therapy.	At time of surgery (approximately within 6 months)
Safety and Tolerability	Incidence and severity of adverse events assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	Up to 36 months

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Weijian Guo, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: GC-CTDNA2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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