Feasibility of Circulating Tumor DNA Based Minimal Residual Disease-Guided Adjuvant Therapy in Locally Advanced Gastric Cancer With Neoadjuvant Treatment: An Adaptive Trial (MRD-ATLAS)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Recurrence-Free Survival (RFS)
研究概览
简要总结
Standard treatment for locally advanced gastric cancer currently involves surgery combined with chemotherapy administered both before and after the operation. However, post-surgery (adjuvant) chemotherapy often causes severe side effects, and it is unclear if all patients truly benefit from it. Recent research, such as the SPACE-FLOT study, suggests that patients who respond well to pre-surgery treatment might not actually benefit from further aggressive treatment after surgery; in these cases, additional therapy may only increase the risk of side effects without improving survival.
To address this, researchers are investigating circulating tumor DNA (ctDNA) testing, which detects microscopic traces of cancer (Molecular Residual Disease, or MRD) in the blood. The utility of ctDNA is supported by extensive research:
In Colorectal Cancer: The GALAXY study demonstrated that ctDNA status accurately predicts patient survival and identifies who benefits from chemotherapy. Furthermore, the DYNAMIC study showed that using ctDNA to guide treatment decisions significantly reduced the use of unnecessary chemotherapy without compromising patient survival.
In Gastric Cancer: Studies such as MENCA-GC, CRITICS, and PLAGAST have confirmed that post-surgery ctDNA is a strong predictor of patient prognosis. Additionally, the MRD-GATE study provided preliminary evidence that ctDNA-guided strategies can reduce unnecessary chemotherapy in the adjuvant setting.
Building on this evidence, this study applies ctDNA testing to the standard perioperative treatment model for gastric cancer. The primary objective is to determine if a ctDNA-guided strategy can identify patients who can safely forgo post-surgery chemotherapy, thereby reducing treatment toxicity and unnecessary usage, without sacrificing long-term survival outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be able to provide a written informed consent form (ICF), and understand, agree to, and comply with the study requirements and assessment schedule.
- •Male or female aged 18 to 79 years.
- •Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction (GEJ), with clinical TNM staging (per the 8th edition of the AJCC/UICC Clinical TNM Staging for Gastric Cancer) as clinical Stage cIII to cIVa, and the primary gastric cancer lesion assessed to be amenable to curative resection.
- •ECOG PS ≤ 2, tolerable to surgical treatment, no surgical contraindications.
- •Females of childbearing potential must have a negative pregnancy test within 7 days prior to initiating neoadjuvant treatment. Males of reproductive potential and females of childbearing potential must agree to use adequate contraceptive measures during the study and for 24 months after the last dose of study medication.
- •Prior to neoadjuvant treatment, complete blood count (CBC) and biochemical tests must meet the following criteria: a) Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; b) Platelet Count (PLT) ≥ 75 × 10⁹/L; c) Hemoglobin (Hb) ≥ 80 g/L; d) Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × Upper Limit of Normal (ULN); e) Serum Creatinine (Cr) ≤ 1.5 × ULN, or Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m²; f) Serum Albumin (ALB) ≥ 30 g/L; g) For subjects not receiving anticoagulant therapy: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN, and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; for subjects receiving anticoagulant therapy: PT value must be within the expected therapeutic range for the anticoagulant used.
- •No antitumor treatment for the tumor involved in the current study has been administered prior to the initiation of neoadjuvant treatment.
排除标准
- •Subjects for whom investigators consider that there are obvious contraindications to (neo)adjuvant treatment or who cannot tolerate (neo)adjuvant treatment.
- •Females of childbearing potential who have not undergone surgical sterilization or do not use adequate contraceptive measures, pregnant or lactating females, and males who plan to impregnate their partners in the near term.
- •Any severe or uncontrolled systemic disease, including but not limited to uncontrolled hypertension, active bleeding, diabetes mellitus, and others.
- •Severe chronic or active infections that require systemic antibacterial, antifungal, or antiviral therapy, including but not limited to tuberculosis (TB), human immunodeficiency virus (HIV) infection, and others.
- •History of previous malignant tumors or other malignant tumors currently present, except for basal cell or squamous cell skin cancer, superficial bladder cancer, prostatic/cervical/breast carcinoma in situ, and other such tumors that have been completely resected with no recurrence for at least 5 years.
- •Other circumstances that investigators deem inappropriate for study participation.
研究组 & 干预措施
Experimental Arm
Participants in this group will receive four cycles of neoadjuvant therapy followed by radical gastrectomy. Postoperatively, patients will be stratified based on their ctDNA MRD status at the post-surgical timepoint:
- ctDNA MRD-Negative Subgroup (estimated n=30): Patients will not receive adjuvant therapy (observation only).
- ctDNA MRD-Positive Subgroup (estimated n=30): Patients will receive adjuvant therapy.
干预措施: Standard neoadjuvant therapy (Drug)
Experimental Arm
Participants in this group will receive four cycles of neoadjuvant therapy followed by radical gastrectomy. Postoperatively, patients will be stratified based on their ctDNA MRD status at the post-surgical timepoint:
- ctDNA MRD-Negative Subgroup (estimated n=30): Patients will not receive adjuvant therapy (observation only).
- ctDNA MRD-Positive Subgroup (estimated n=30): Patients will receive adjuvant therapy.
干预措施: Radical gastrectomy (Procedure)
Experimental Arm
Participants in this group will receive four cycles of neoadjuvant therapy followed by radical gastrectomy. Postoperatively, patients will be stratified based on their ctDNA MRD status at the post-surgical timepoint:
- ctDNA MRD-Negative Subgroup (estimated n=30): Patients will not receive adjuvant therapy (observation only).
- ctDNA MRD-Positive Subgroup (estimated n=30): Patients will receive adjuvant therapy.
干预措施: ctDNA-MRD-guided adjuvant therapy (Drug)
Control Arm
This group serves as a standard-of-care comparison. Participants will receive four cycles of neoadjuvant therapy followed by radical gastrectomy. The decision to administer postoperative adjuvant therapy will be made by experienced clinicians based on standard treatment guidelines and the patient's individual condition.
This group will include participants who meet any of the following criteria:
- Patients who decline ctDNA-guided postoperative adjuvant therapy strategies.
- Patients for whom insufficient tumor tissue was collected during screening to complete Whole Exome Sequencing (WES).
- Patients who are unwilling or unable to provide sufficient peripheral blood samples for ctDNA MRD testing.
- Any other conditions deemed unsuitable for inclusion in the Experimental Arm by the investigator.
干预措施: Standard neoadjuvant therapy (Drug)
Control Arm
This group serves as a standard-of-care comparison. Participants will receive four cycles of neoadjuvant therapy followed by radical gastrectomy. The decision to administer postoperative adjuvant therapy will be made by experienced clinicians based on standard treatment guidelines and the patient's individual condition.
This group will include participants who meet any of the following criteria:
- Patients who decline ctDNA-guided postoperative adjuvant therapy strategies.
- Patients for whom insufficient tumor tissue was collected during screening to complete Whole Exome Sequencing (WES).
- Patients who are unwilling or unable to provide sufficient peripheral blood samples for ctDNA MRD testing.
- Any other conditions deemed unsuitable for inclusion in the Experimental Arm by the investigator.
干预措施: Radical gastrectomy (Procedure)
Control Arm
This group serves as a standard-of-care comparison. Participants will receive four cycles of neoadjuvant therapy followed by radical gastrectomy. The decision to administer postoperative adjuvant therapy will be made by experienced clinicians based on standard treatment guidelines and the patient's individual condition.
This group will include participants who meet any of the following criteria:
- Patients who decline ctDNA-guided postoperative adjuvant therapy strategies.
- Patients for whom insufficient tumor tissue was collected during screening to complete Whole Exome Sequencing (WES).
- Patients who are unwilling or unable to provide sufficient peripheral blood samples for ctDNA MRD testing.
- Any other conditions deemed unsuitable for inclusion in the Experimental Arm by the investigator.
干预措施: Standard adjuvant therapy (Drug)
结局指标
主要结局
Recurrence-Free Survival (RFS)
时间窗: From completion of adjuvant therapy (or radical gastrectomy for patients not receiving adjuvant therapy) up to 2 years, assessed every 3 months.
RFS is defined as the time from the date of radical gastrectomy to the date of the first documented disease recurrence or death from any cause.
次要结局
- Overall Survival (OS)(From completion of adjuvant therapy (or radical gastrectomy for patients not receiving adjuvant therapy) up to 2 years, assessed every 3 months.)
- ctDNA Clearance Rate(Within 7 days prior to the initiation of neoadjuvant therapy. Within 7 days prior to radical gastrectomy. 3 to 5 weeks post-surgery. 4 weeks after completion of adjuvant therapy, or 5 months post-surgery.)
- The time point of ctDNA conversion from negative to positive and the time difference from the time point of radiological diagnosis of tumor recurrence(Within 7 days prior to radical gastrectomy. 3 to 5 weeks post-surgery. 4 weeks after completion of adjuvant therapy, or 5 months post-surgery.)
- Pathological Complete Response (pCR) Rate(Within 1 week after radical gastrectomy)
研究者
Xuefei.Wang
Chief of Department of Gastrointestinal Surgery
Shanghai Zhongshan Hospital