A Feasibility Study for Convernsion Therapy Using S1/Paclitaxel Chemotherapy Plus Apatinib in ELM Gastric Cancer

Study Overview
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Brief Summary
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The prognosis of Extensive lymph nodes metastatic(ELM) gastric cancer is poor. Chemotherapy occasionally converts it to a resectable cancer. Previous studies showed patients with ELM gastric cancer may obtain a survival benefit from chemotherapy and subsequent curative surgery. The key of conversion therapy of ELMGC is the high response rate. Apatinib, a novel targeted inhibitor of VEGF receptor 2 (VEGFR2), shows significant antitumor activity in the patients with GC. On the basis of our previous Ahead-G325 study, The purpose of this study is to investigate the efficacy and safety of S1/Paclitaxel chemotherapy plus Apatinib in the conversion therapys of ELM gastric cancer.

Detailed Description
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The investigators will apply SPA regimen for coversional therapy to abtain high response rate. Paclitaxel：150 mg/m2 i.v.3h , given on the first day. Apatinib, oral ,initial dose :425mg, QD, after meal ( try to take the medicine at the same time of the day ). Dose adjustment: Down-regulate the dosage to 250 mg per day at the first time. If the patient totally recovers from the toxic reaction after the regulation, we could up-regulate the dosage back to the former level. If the downregulation occurs again according to the protocol , then the up-regulation will be forbidden. S-1 dosage: According to the body surface area, the initial dosage of S-1 is decided by the following criteria. Take the medicine twice daily (after breakfast and supper) for 2 weeks, then suspend for 1 week. Preventive medication: To prevent serious allergic reaction of Paclitaxel, preventive medication should be given in advance. We usually give dexamethasone 20mg orally 12 and 6 hours before the Paclitaxel, and diphenhydramine (or something analogous) 50 mg, cimetidine 300mg (or ranitidine 50mg) I.V. 30-60 minutes before the Paclitaxel. Repeat the therapeutic schedule every 3 weeks. 3-4 cycles of neoadjuvant chemotherapy before surgery, stop Apatinib in the last cycle.4 cycles of adjuvant chemotherapy including S-1 and Apatinib 4 to 6 weeks after surgery.

Official Title
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Phase II Study of Convernsion Therapy Using S1/Paclitaxel Chemotherapy Plus Apatinib in ELM Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: SPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ELM gastric cancer as proven histologically under following condition: unable radical excision due to the abdominal aorta a2-b1 or extensive lymph nodes metastatic, Definitely diagnosed as above stage of gastric cancer before operation via CT of MRI, ultrasonic endoscopy, PET-CT, or through the laparoscopic exploration if necessary Untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy) Negative HER-2 state ECOG(Eastern Cooperative Oncology Group): 0 2 Age: 18 70 years old- survival time > 3monts Normal hemodynamic indices before the recruitment(including blood cell count and liver/kidney function ). For example: WBC>4.0*109/ L, NE>1.5*109/L, PLT>100*109/L, BIL<1.5 times of upper limit of normal reference value, ALT and AST<2.5 times of upper limit of normal reference value, and CRE<1.2mg/dl Good cardiac function before the recruitment, no seizure of myocardial infarction in past half years, and controllable hypertension and other coronary heart disease Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver) Not participating in other clinical trials before and during the treatment Signed the Informed Consent Form No peritoneal metastatic and CY0 in 28 days by laparoscopic exploration Non-gastric stump cancer No esophagus infiltrating or infiltrating less than 3cm Exclusion Criteria: Distal metastasis to Mediastinal lymph node,liver ,peritoneal,pleural effusion ,ascites,above 16a2-b1 and others Severe mental illness Her-2 positive, desire for hercptin treatment Ever administrated with other drugs(including TCM drugs) before the recruitment, or no guarantee of progress according to the study requirement after recruitment Allergy to the drugs in this protocol Pregnant and lactating women Women at childbearing age and of pregnancy desire during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conversion treatment<br>after 3-4 cycles S1/Paclitaxel chemotherapy plus Apatinib,subsequent surgery will be conducted with curative intent. | Drug: SPA<br>* S1/Paclitaxel chemotherapy plus Apatinib S1:60mg twice daily(after the breakfast and supper) for two weeks, and then suspend for one week Paclitaxel:150mg/m2,iv, 3h, at day1 Apatinib:425mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year OS | The overall survival time | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radical resection rate | the radical resection rates | 4 months | 
| 3 year DFS | the diesease free survival time | 3 years | 
| 5 year OS | The overall survival time | 5 years | 
| adverse events | number and degree of adverse events | 7months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conversion therapy