Gastric Cancer
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTCirculating 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.
DRUGStandard 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.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 36 months | 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. |
| Overall Survival (OS) | Up to 36 months | Overall survival (OS) is defined as the time from study enrollment to death from any cause. |
| Disease Control Rate (DCR) | Up to 24 months | 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. |
| Recurrence-Free Survival (RFS) | Up to 36 months | Recurrence-free survival (RFS) is defined as the time from study enrollment (or surgery for applicable patients) to the first documentation of disease recurrence. |
| Pathological Complete Response Rate (pCR) | At time of surgery (approximately within 6 months) | Pathological complete response (pCR) is defined as the absence of residual tumor cells in the resected specimen after neoadjuvant or conversion therapy. |
| Safety and Tolerability | Up to 36 months | Incidence and severity of adverse events assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
Countries
China
Contacts
CONTACTWeijian Guo
PRINCIPAL_INVESTIGATORWeijian Guo
Fudan University
Outcome results
None listed