A Prospective Phase II Study of Dynamic Circulating Tumor DNA to Predict and Guide Systemic Treatment in Patients With Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years. Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •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.
- •Pathological stage II-III disease without distant metastasis.
- •Planned to receive standard adjuvant chemotherapy (e.g., XELOX or SOX).
- •Advanced Disease Cohort:
- •14. Unresectable or metastatic disease not amenable to curative surgery.
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Circulating Tumor DNA (ctDNA) Analysis (Diagnostic Test)
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.
干预措施: Standard Systemic Therapy for Gastric Cancer (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 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.
次要结局
- Progression-Free Survival (PFS)(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)
- Disease Control Rate (DCR)(Up to 24 months)
- Recurrence-Free Survival (RFS)(Up to 36 months)
- Pathological Complete Response Rate (pCR)(At time of surgery (approximately within 6 months))
- Safety and Tolerability(Up to 36 months)
研究者
Weijian Guo
Chief Physician
Fudan University