Recently, growing evidences have suggested that immunotherapy represents a promising treatment option for the neoadjuvant treatment of locally advanced mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer. In this study, we will explore the efficacy and safety of sintilimab and LDRT in the neoadjuvant treatment for locally advanced dMMR/MSI-H G/GEJ cancer.
This is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib, 4 cases will be enrolled in each treatment group. In the phase II study, a total of 33 patients will be enrolled. Eligible patients will be registered and receive four cycles of sintilimab. Simultaneously, LDRT will be planned and administered. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of sintilimab. The primary endpoint of phase Ib is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pathological complete response (pCR) rate. Secondary endpoints include R0 resection rate, major pathological response (MPR), objective response rate (ORR), 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate and safety profile of the neoadjuvant regimen.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
All patients will start with one cycle of neoadjuvant therapy of sintilimab: sintilimab 200 mg, iv drip, d1, q3w. LDRT will be performed in the target area. After radiotherapy, patients will receive another three cycles of sintilimab. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of sintilimab. The adjuvant therapy will start in 4-6 weeks after the surgery, and we recommend adjuvant treatment with sintilimab for up to 10 cycles.
pCR rate
defined as the absence of viable tumor cells assessed by histological evaluation criteria after neoadjuvant therapy
Time frame: 5 months after the last subject participating in
R0 resection rate
defined as the rate of the complete surgical removal of any residual cancer cells in the tumor bed
Time frame: 5 months after the last subject participating in
MPR rate
defined as tumor residual cells ≤10% in the surgical specimen
Time frame: 5 months after the last subject participating in
3-year event-free survival (DFS)
defined as the proportion of patients without event 23 years after enrolment
Time frame: every 3 month postoperation up to 36 months
2-year OS rate
defined as the proportion of patients survived 3 years after enrolment
Time frame: every 3 month postoperation up to 36 months
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