A Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Chemoradiotherapy in Gastric Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
This prospective, randomized phase II study is designed to evaluate weather neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy with both followed by surgery and postoperative chemotherapy for locally advanced gastric adenocarcinoma.

Official Title
-----------------
A Prospective, Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Concomitant Boost Intensity-Modulated Radiotherapy With S-1 in Locally Advanced Gastric Adenocarcinoma

Conditions
-----------------
Stomach Neoplasms, Neoadjuvant Therapy, Chemoradiotherapy, Chemotherapy

Intervention / Treatment
-----------------
* Radiation: SIB-IMRT
* Drug: S-1
* Procedure: Surgery
* Drug: SOX


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically proven locally advanced gastric adenocarcinoma in patients staged as cT3-4N0M0 or anyTN+M0 No distant metastasis in liver,lung,bone,central nervous system(CNS),no peritoneal transplantation No prior abdominal or pelvic radiotherapy Karnofsky performance status(KPS)≥ 70, predictive life span no less than 6 months Patients must have normal organ and marrow function as defined below: Leukocytes: greater than or equal to 3,000 G/L; Platelets: greater than or equal to 100,000/mm3 .Hemoglobin:greater than or equal to 10g/L .Total bilirubin: within normal institutional limits; AST/ALT: less than or equal to 1.5 times the upper limit; Creatinine within normal upper limits Informed consent Exclusion Criteria: Any prior chemotherapy or other cancer treatment prior to this protocol Patients with other cancer history except cervical carcinoma in situ and non-malignant melanoma skin cancer With any distant metastasis in liver,lung,bone,CNS,or peritoneal transplantation History of allergic reactions attributed to similar chemical or biologic complex to S-1 or Xeloda or Oxaliplatin Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness History of myocardial infarction within the past 6 months or history of ventricular arrhythmia History of prior radiation to the abdomen Pregnant or lactating females

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant Chemoradiotherapy (NCRT)<br>NCRT arm receives intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) (45.1Gy and 40.04Gy in 22 fractions) concurrently with oral S-1(40mg/m2, orally twice daily every weekday) followed by surgery and four to six cycles of SOX at the same dosage with NCT arm. | Radiation: SIB-IMRT<br>* 45.1Gy and 40.04Gy in 22 fractions using intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) to primary tumor<br>Drug: S-1<br>* 40mg/m2, orally twice daily every weekday concurrently with radiotherapy treatment<br>* Other names: TS-1;Procedure: Surgery<br>* Surgery, preferred D2 lymphadenectomy<br>Drug: SOX<br>* SOX (S-1: 40 60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle)<br>* Other names: TS-1; Oxaliplatin for injection;|
| Active Comparator: Neoadjuvant Chemotherapy (NCT)<br>NCT arm consists of neoadjuvant three cycles of SOX(S-1: 40 60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle followed by radical surgery and another postoperative three cycles of SOX. | Procedure: Surgery<br>* Surgery, preferred D2 lymphadenectomy<br>Drug: SOX<br>* SOX (S-1: 40 60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle)<br>* Other names: TS-1; Oxaliplatin for injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | The surgical procedure was total or subtotal gastrectomy with recommended D2 lymphadenectomy 4-6 weeks after neoadjuvant therapy. | 2-3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | Pathological response were classiﬁed into three grades.Grade I signiﬁes that there is little shrinkage in the tumor; only mild regression in the tumor cells is observed under themicroscope. Grade II shows gross reduction in size of the tumor and marked regression in the cancer cells microscopically, yet viable nests of cancer tissue are still visible. Grade III implies complete or almost total resolution of the tumor on exploration, and disappearance of the tumor tissue microscopically; only remnants of degenerated cancer cells can be seen (so-called ghost cancer cells). | 2-3 months | 
| Tumor down-staging | Down-staging was considered as any stage reduction between clinical and pathologic stage. | 2-3 months | 
| Postoperative complications | During hospital stay and within the first 30 days after completion of surgery. | 2-3 months | 
| Acute chemotherapy/Chemoradiotherapy toxicities | chemotherapy toxicities are evaluated by NCI-CTC version 4.0 and radiotherapy toxicities are graded using the RTOG/EORTC Radiation Morbidity Scoring Schema. | 6-8 months | 
| Distant metastasis free survival |  | 3 years | 
| Locoregional recurrence free survival |  | 3 years | 
| Overall survival |  | 3 years |