The goal of this clinical trial is to evaluate postoperative adaptive adjuvant therapy in patients with gastric or gastroesophageal junction adenocarcinoma after neoadjuvant chemotherapy plus immunotherapy and radical gastrectomy.The main questions it aims to answer are: 1. In patients with poor pathological response, does switching to a alternative postoperative treatment regimen improve survival? 2. In patients with complete pathological response, can observation without routine postoperative treatment maintain favorable survival outcomes? Participants will be assigned to different cohorts according to their pathological response after surgery and will be followed regularly for recurrence, survival, and treatment-related side effects.
This prospective clinical trial will enroll patients with gastric or gastroesophageal junction adenocarcinoma who have received neoadjuvant chemotherapy plus immunotherapy followed by radical gastrectomy. Participants will be assigned to predefined cohorts according to postoperative pathological response and pathological stage. Patients with poor pathological response, defined as TRG 3 and ypT3-4N2-3M0 disease, will be evaluated to determine whether switching to a alternative postoperative treatment regimen improves survival and remains safe compared with continuing the original treatment regimen. For patients with complete pathological response, defined as TRG 0 and ypT0N0M0 disease, will be evaluated to determine whether observation without routine postoperative treatment maintain favorable survival outcomes. The study aims to assess whether postoperative treatment can be adapted according to pathological response after neoadjuvant therapy, rather than applying the same postoperative treatment strategy to all patients. The results may help develop more individualized postoperative management strategies for patients at very high or very low risk of recurrence after neoadjuvant therapy and radical surgery.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
405
Participants in this arm will switch to an alternative postoperative treatment regimen selected by the investigator according to prior neoadjuvant therapy, postoperative molecular subtype, and the 2025 CSCO and NCCN guidelines. The regimen will include taxane-based or irinotecan-based treatment that was not used before surgery, with dosage and administration based on clinical practice standards and drug prescribing information.
The original preoperative treatment regimen will be continued postoperatively. The administration schedule and dosage of adjuvant therapy will follow standard clinical practice guidelines and the relevant drug prescribing information.
Participants will undergo postoperative observation without further antitumor drug therapy. Routine follow-up monitoring will be conducted according to the study protocol.
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China
Median Event-Free Survival in Cohort 1(mEFS)
defined as the time from randomization to the first documented local, regional, or distant recurrence, or death from any cause, whichever occurs first.
Time frame: Up to approximately 13 months
2-year Event-Free Survival Rate in Cohort 2(2-y EFS)
defined as the proportion of participants in Cohort 2 who are alive without documented local, regional, or distant recurrence at 2 years after cohort assignment.
Time frame: Up to 2 years
1-year Event-Free Survival Rate in Cohort 1(1-y EFS)
defined as the proportion of participants in Cohort 1 who are alive without documented local, regional, or distant recurrence at 1 year after randomization.
Time frame: Up to 1 year
1-Year Overall Survival Rate in Cohort 1(1-y OS)
defined as the proportion of participants in Cohort 1 who are alive at 1 year after randomization.
Time frame: Up to 1 year
Median Overall Survival in Cohort 1(mOS)
defined as the time from randomization to death from any cause. Median overall survival will be evaluated in participants in Cohort 1.
Time frame: Up to approximately 3 years
2-Year Overall Survival Rate in Cohort 2(2-y OS)
defined as the proportion of participants in Cohort 2 who are alive at 2 years after cohort assignment.
Time frame: Up to 2 years
3-year Event-Free Survival Rate in Cohort 2(3-y EFS)
defined as the proportion of participants in Cohort 2 who are alive without documented local, regional, or distant recurrence at 3 years after cohort assignment.
Time frame: Up to 3 years
3-year Overall Survival Rate in Cohort 2(3-y OS)
defined as the proportion of participants in Cohort 2 who are alive at 3 years after cohort assignment.
Time frame: Up to 3 years
Incidence and Severity of Adverse Events
The incidence and severity of adverse events will be assessed according to NCI CTCAE version 5.0. Safety assessments will include adverse events, serious adverse events, vital signs, ECOG performance status, physical examination, electrocardiogram, echocardiography, and clinically significant changes from baseline in laboratory test results.
Time frame: Up to approximately 3 years
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