To evaluate efficacy and safety of Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) in resectable locally advanced gastric cancer.
This is a single-arm clinical study to enroll 50 patients with gastric cancer (cTNM diagnosis of cT3-4aN1-3M0). Each enrolled patient will be assigned a case number. Both this case number and the patient's initials will be entered on each page of the case report form. Enrolled patients receive a neoadjuvant regimen of POLF in combination with sindilizumab: preoperatively, they receive a POLF regimen (paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, and 5-fluorouracil 425 mg/m2) administered once weekly for a total of 6 doses, and in combination with sindilizumab 200 mg intravenously once every 3 weeks for a total of 2 doses. Upon completion of the evaluation, patients whose tumors were judged to be resectable underwent radical surgery and received six postoperative doses of the POLF regimen and two doses of Sindilizumab as adjuvant therapy. Postoperative imaging evaluations will be performed every three months until disease recurrence. Survival follow-up was performed every three months after disease recurrence. Patients will receive neoadjuvant therapy for 6 weeks preoperatively and adjuvant therapy for 6 weeks postoperatively unless intolerable toxicity occurs, the patient refuses to continue treatment, or treatment is delayed beyond 3 weeks. Patients will be under study observation during treatment and 30 days after treatment termination, and will receive long-term follow-up for 5 years postoperatively. Ultimately, pCR and MPR will be the primary study endpoints, and ORR, DCR, 2-year PFS rate, 3-year OS rate and safety will be the secondary study endpoints to evaluate the efficacy and safety of the neoadjuvant regimen of POLF combined with sindilizumab, as well as to explore the immune activation effect and mechanism of the regimen using peripheral blood and tumor tissue samples.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Drug: Sintilimab 200mg iv d1 Q3W, 2cycles Drug: Paclitaxel 60 mg/m2, d1, QW,6cycles Drug: Oxaliplatin 50 mg/m2, d1, QW, 6cycles Drug: 5-fluorouracil 425mg/m2 ,d1 ,QW, 6cycles
Huashan Hospital, Fudan University
Shanghai, China
RECRUITINGPercentage of participants with no residual surviving tumor cells in resection specimens and lymph nodes
Pathological complete response rate (pCR), defined as the proportion of participants with no residual viable tumor cells on microscopy and negative lymph nodes as a percentage of all participants. We will evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.
Time frame: up to 6 weeks after first dosing
Percentage of participants with ≤10% tumor cell survival in resection specimens
Major pathologic response (MPR) rate, defined as the proportion of participants with ≤10% surviving tumor cells in the resection specimen as a percentage of all participants. We will evaluate major pathological response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.
Time frame: up to 6 weeks after first dosing
Percentage of participants achieving complete remission (CR) and partial remission (PR) after treatment
Objective remission rate (ORR), the percentage of participants whose tumors shrink by a certain amount and remain there for a certain period of time, including complete remission (CR) and partial remission (PR). CR (Complete remission): Complete disappearance of the target lesion, with no new lesions produced, and lasting for more than 4 weeks. PR (Partial remission): the sum of the largest diameters of the target lesions is reduced by more than 30%, and lasts for more than 4 weeks.
Time frame: 2 to 6weeks after the end of treatment
Percentage of participants achieving remission (PR+CR) and lesion stabilization (SD) after treatment
Disease control rate (DCR) is the percentage of participants who achieve remission (PR+CR) and stabilization of lesions (SD) after the treatment. Stable disease (SD) means that the sum of the largest diameters of the tumor lesions has not shrunk to PR, or has not enlarged to PD.
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Time frame: 2 to 6weeks after the end of treatment
2-year progression-free survival (PFS) rate
Percentage of participants who survived or were free of tumor progression from enrollment to the second year of follow-up.
Time frame: From enrollment to study completion, assessed up to 2 years
3-year overall-survival (OS) rate
Percentage of participants who survived from enrollment to the third year of follow-up.
Time frame: From enrollment to study completion, assessed up to 3 years
Number of participants with treatment-related adverse events as assessed by NCI-CTC
Toxicity deaths and early withdrawal from treatment due to toxic effects will be described. Toxicity assessment of adverse events and serious adverse events (SAEs) using the NCI-CTC.
Time frame: From enrollment to study completion, assessed up to 3 years