XELOX Combined With Apatinib as Post-operative Chemotherapy in Locally Advanced Gastric Adenocarcinoma

To observe and evaluate the efficacy and safety of oxaliplatin with oapecitabine（XELOX）combined with apatinib as post-operative chemotherapy in locally advanced gastric adenocarcinoma with D2 dissection

Stage 1 (phase I tolerance study) : 12 patients were enrolled in the dose-climbing study:According to the principle of dose-climbing test,todetermine the subjects' MTD, with the following three dose levels:

* Capecitabine: 1000 mg/m2 bid d1-14 q3w, oxaliplatin: 130 mg/m2 d1 q3w) + apatinib 250 mg, qd x180d; ②. Capecitabine: 1000 mg/m2 bid d1-14 q3w, oxaliplatin: 130 mg/m2 d1 q3w) + apatinib 375 mg, qd x180d; ③. Capecitabine: 1000 mg/m2 bid d1-14 q3w, oxaliplatin: 130 mg/m2 d1 q3w) + apatinib 500 mg, qd x180d;

Stage 2 (phase II exploratory study) :

①.Test group: subjects received 8 cycles of postoperative XELOX regimen (capecitabine: 1000 mg/m2 bid d1-14 q3w, oxaliplatin: 130 mg/m2 d1 q3w) + apatinib maximum tolerated dose

②.Control group: Subjects received 8 cycles of XELOX regimen after surgery (capecitabine: 1000 mg/m2 bid d1-14 q3w, oxaliplatin: 130 mg/m2 d1 q3w).

Eligible patients will receive 8 cycles of postoperative adjuvant therapy and will be followed up to death

Eligibility Criteria:
Inclusion Criteria:

1. ECOG score is 0-1;
2. Radical gastrectomy (D2, R0) for gastric cancer has been performed (more than 16 lymph nodes have been detected);
3. Postoperative histology confirmed gastric adenocarcinoma；
4. The pathological stage of gastric cancer is ⅢA-ⅢC stage (8th AJCC TNM);
5. Subjects' baseline blood routine and biochemical indicators meet the following standards:

   * ANC≥1.5×109/L;
   * Hb≥90g/L;
   * PLT≥100×109/L;
   * TBIL≤1.5×ULN;
   * ALT and AST≤2×ULN;
   * Cr≤1.5×ULN
   * INR：1.0～1.5; APTT is within the normal range
6. The electrocardiogram was basically normal before the first 4 weeks after admission, and there were no obvious clinical symptoms of heart disease;
7. Sign informed consent.

Exclusion Criteria:

1. Patients with severe hypertension and poor drug control;
2. Various factors that affect oral drugs such as (inability to swallow, complete or incomplete gastrointestinal obstruction, active gastrointestinal bleeding, perforation ) ;
3. Patients with previous bradycardia or prolonged QT interval;
4. Patients with postoperative gastrointestinal fistula and wound rupture;
5. Known allergy to capecitabine or oxaliplatin, or metabolic disorder;
6. Patients receiving preoperative chemotherapy, radiotherapy or targeted therapy before;
7. Patients Using other experimental drugs at the same time or joining in other clinical trials.
8. Patients with severe liver diseases (such as liver cirrhosis), nephropathy, respiratory diseases or chronic systemic diseases such as uncontrollable diabetes and hypertension; Clinical symptoms of heart disease,such as congestive heart failure,coronary heart disease symptoms, arrhythmia, hypertension,that hard to control,or having myocardial infarction attack in six months or cardiac insufficiency.
9. Patients with peripheral nervous system disorder or with a history of significant psychiatric disorder and central nervous system disorder;