1. Target population: patients with resectable locally advanced gastric cancer (cT3-4bN+M0). 2. Primary objective: (1) To evaluate the pathological remission rate (PRR) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer. (2) To evaluate the relationship between tumor pathological remission and biomarkers related to immunotherapy. 3\. Secondary objectives: 1. To evaluate the imaging objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of PD-1 antibody alone or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant therapy for locally advanced gastric cancer. 2. To evaluate the safety of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer. Trial design: This is a monocenter, open, single arm, phase II study to evaluate the efficacy and safety of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant treatment of resectable locally advanced gastric cancer.
Several important clinical trials including MAGIC, FLOT4, POET, RTOG 9904 and TOPGEAR have identified the efficacy and safety of neoadjuvant treatment in treating locally advanced GEJ cancer or gastric cancer. patients with resectable locally advanced gastric cancer will receive neoadjuvant treatment of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin. The investigators will shut down the study in advance, if situations below happens: 1) 1 treatment related death, \>3 disease progression or \>2 hyper-progressive disease happen during the first stage; 2) 2 treatment related death, \>6 disease progression or \>4 hyper-progressive disease happen during the whole study. Patients with abnormal autoimmune status, unfavorable body function, factors impeding drug taking, absorption and metabolism will be excluded. Study participants with disease progression or severe/ intolerant toxicity during treatment will withdraw the study. Hyper-progressive disease is defined as 1) progression 2) more than doubled growth rate 3) tumor volume increase \>50% in 2 months after initialing the treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
The patients will receive at least two cycles of SHR-1210 (200 mg, invdrip d1) every two weeks and be accessed for operational suitability every two cycles.
The patients will received apatinib (250mg po qd) until 10 ± 2 days before surgery.
The patients will received S1 (50 mg/m2, po, bid, d1-d10) every two weeks and be accessed for operational suitability every two cycles.
The patients will receive at least two cycles of oxaliplatin (85 mg/m2 d1) every two weeks and be accessed for operational suitability every two cycles.
Qilu hospital of Shandong univertisy
Jinan, Shandong, China
Pathological remission rate (PRR) rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
The pathological response was calculated according to the proportion of residual viable tumor cells in the tumor bed. Complete pathological response (CPR) was defined as no residue tumor cells. Major pathological response (MPR) was defined as less than 10% residue tumor cells.
Time frame: 5 months after the last subject participating in
Immunotherapy-related biomarkers
To evaluate the relationship between tumor pathological remission and immunotherapy related biomarkers, including tumor genome, tumor microenvironment and host immune system response biomarkers.
Time frame: 5 months after the last subject participating in
objective response rate (ORR) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1. However, responses do not require confirmation according to RECIST v 1.1. ORR was evaluated by chest, abdominal \& pelvic CT/MRI.
Time frame: Time Frame: 36 months after the last subject participating in
progression free survival (PFS)of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
PFS is defined as time interval from recruitment to tumor progression. Tumor progression is defined as below: 1) tumor re-occurrence, 2) death, 3) censoring, and 4) beginning to use any other anti-tumor medicines.
Time frame: Time Frame: 36 months after the last subject participating in
overall survival (OS) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
OS is defined as time interval from recruitment to all-caused death or censoring.
Time frame: Time Frame: 36 months after the last subject participating in
safety as measured by the rate of adverse events (AEs), laboratory abnormalities, dose adjustment, discontinuation of administration, early discontinuation of the study drug, and delay to surgery.
Adverse events (AEs) of neoadjuvant therapy will be graded and documented according to NCI-CTCAE v4.0 from the beginning of treatment to 1 months after the last date of treatment. Documentary will include severity, lasting period and occurrence time. Main AEs include vomiting, diarrhea, anemia, leukopenia, thrombocytopenia, hand-foot syndrome, epidermal capillary hyperplasia, immune related adverse events (including pneumonia, interstitial lung disease, AST/ALT elevations, rash, diarrhea, hypothyroidism and hyperthyroidism) and hyper-progressive tumor. AEs of surgery refer to complications which happen during or in 30 days after operation. Severe complications after operation such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, incision complications (infection, bleeding, rupture) will be observed and classified by Clavien-Dindo grading.
Time frame: Time Frame: 1 month after the last date of treatment
R0 resection rate
To evaluate the R0 resection rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Time frame: 5 months after the last subject participating in
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