Oxaliplatin Plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma
Oxaliplatin Plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma
1. Target population:locally advanced gastric adenocarcinoma (LAGC, cT2~3/N+M0,or
 cT4aN+M0);no previous chemo or radio therapy.

 2. Primary objective:Response rate of XELOX in the neoadjuvant setting of LAGC.

 Secondary objectives:

 -  The progression free survival (PFS) in the perioperative treatment of locally
 advanced gastric adenocarcinoma (cT3/N+M0,or cT4aN+M0);

 -  percentage of pathological response ; percentage of grade 3 or 4 adverse events as
 safety profile of perioperative treatments;

 -  D2 resection -rate after neoadjuvant chemotherapy of XELOX;

 -  Overall survival;

 -  QOL during the whole period of treatment.

 3. Trial design:This is a multicenter, single arm, open-label, phase II study to evaluate
 the efficacy and safety of Oxaliplatin plus capecitabine(XELOX) in the perioperative
 treatment of locally advanced gastric adenocarcinoma in combination with D2 resection.

 4. Treatment plan:Patients will be given the perioperative chemotherapy as below once
 recruited:Schedule of Oxaliplatin plus capecitabine (XELOX) will be as follow:
 Capecitabine 1000 mg/m2 ，bid,d 1~14 every 3 weeks(treatment for 2 weeks and rest 1
 week)Oxaliplatin：130mg/m2， iv infusion over 2h，d1,every 3 weeks.

 5. Number of subjects:50 patients.Number of centers 5 sites, which have the high volume of
 gastric operations in China, more than 500 per year.
1. Disease specific inclusion criteria:

 -  Histologically documented gastricadenocarcinoma with Lauren classification
 Clinically diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and
 resectable

 -  Measurable disease is required

 -  Karnofsky score 80%.

 -  Physical condition and adequate organ function to ensure the success of abdominal
 surgery.

 -  Life expectancy ≥12 weeks.

 -  Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 ×
 109/L and Hemoglobin ≥8g/dL .Adequate liver function: Total bilirubin ≤ 1.5 × upper
 limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of
 liver metastases, or < 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit
 of normal (ULN); ALB ≥30g/L.

 Adequate renal function: Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60
 ml/min.

 -  Female subjects should not be pregnant or breast-feeding.

 -  No serious concomitant disease that will threaten the survival of patients to less
 than 5 years.

 2. General inclusion criteria:

 -  Male or female. Age ≥ 18 years and ≤75 years

 -  Written (signed) informed consent.

 -  Able to comply with study and follow-up procedures.

 -  Good compliance with the treatment plan。

 -  Consent to provide tissue sample。
Inclusion Criteria:

 -  Histologically documented gastricadenocarcinoma with Lauren classification Clinically
 diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and resectable

 -  Measurable disease is required

 -  Karnofsky score 80%.

 -  Physical condition and adequate organ function to ensure the success of abdominal
 surgery.

 -  Life expectancy ≥12 weeks.

 -  Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 ×
 109/L and Hemoglobin ≥8g/dL .Adequate liver function: Total bilirubin ≤ 1.5 × upper
 limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver
 metastases, or < 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of
 normal (ULN); ALB ≥30g/L.Adequate renal function: Serum creatinine ≤ 1.25 x ULN, and
 creatinine clearance ≥ 60 ml/min.

 -  Female subjects should not be pregnant or breast-feeding.

 -  No serious concomitant disease that will threaten the survival of patients to less
 than 5 years.

 -  Male or female.

 -  Age ≥ 18 years and ≤75 years

 -  Written (signed) informed consent.

 -  Able to comply with study and follow-up procedures.

 -  Good compliance with the treatment plan.

 -  Consent to provide tissue sample.

 Exclusion Criteria:

 -  Pregnant or lactating (in case of potentially childbearing woman, pregnancy test is
 positive)

 -  Patients of child-bearing age or the potential to father a child who refuse to use
 adequate contraception

 -  Serious concomitant disorders that would compromise the safety of the patient or
 compromise the patient's ability to complete the study, at the discretion of the
 investigator.

 -  History of another malignancy in the last 5 years with the exception of the following:

 Any previous palliative, adjuvant or neoadjuvant chemotherapy and/or radiotherapy. Prior
 treatment for locally advanced or metastatic gastric cancer. Any metastatic disease will
 render patient ineligible according to AJCC staging manual.

 -  Distant metastases (M1) including distant nodal Groups (peripancreatic, para-aortic,
 portal, retroperitoneal, mesenteric node, by CT/MRI, or PET/CT

 -  Treatment within the last 30 days with any investigational drug. Concurrent
 administration of any other cancer therapy, including cytotoxic chemotherapy, hormonal
 therapy, and immunotherapy.

 -  Active infection that in the opinion of the investigator would compromise the
 patient's ability to tolerate therapy.

 -  Poorly controlled diabetes mellitus with fasting blood sugar > 18 mM. Second primary
 malignancy that is clinically detectable at the time of consideration for study
 enrollment.

 -  History of significant neurological or mental disorder, including seizures or
 dementia, which would interfere compliance and sign of consent inform. any history of
 hypersensitivity to 5-fluorouracil or platinum and other investigational drug

 -  Ileus, chronic inflammatory intestinal disease or extensive resection of the small
 intestine and other disorders which limit drug reabsorption. This includes gastric
 dumping syndrome, indications of accelerated passage through the small intestine,
 indications of reabsorption disorders after intestinal surgery

 -  Unstable, persistent cardiac disease despite medicinal treatment, myocardial
 infarction within 6 months before the start of the trial

 -  Organ transplant patient need immunosuppression treatment.

 -  Previous surgery on primary tumour; Prior palliative surgery (open and closure,
 passage operation)

 -  Any other type of tumour (e.g. leiomyosarcoma, lymphoma) or a secondary malignancy,
 excepting basal cell skin carcinoma or basal cell carcinoma in situ of the cervix
 which have already been successfully treated

 -  Symptomatic peripheral neuropathy NCI CTC version> 3.0 grade.

 -  Patients under anticoagulant therapy with warfarin or other coumarines are excluded
 from participation.