A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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This prospective, single arm phase II study is designed to evaluate the rate of pathologic complete response of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy followed by surgery for locally advanced gastric adenocarcinoma

Official Title
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A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Gastric Cancer

Conditions
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Gastric Cancer, Neoadjuvant Therapy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven locally advanced gastric adenocarcinoma in patients staged as cT3-4N+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
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Total Neoadjuvant Chemoradiotherapy<br>Total neoadjuvant chemoradiotherapy arm receives intensity-modulated neoadjuvant chemoradiotherapy (45Gy in 25 fractions) concurrently with oral S-1(40-60mg/m2, orally twice daily every weekday) followed by six cycles of SOX neoadjuvant chemotherapy and surgery | Radiation: SIB-IMRT<br>* 45Gy in 25 fractions using intensity-modulated radiotherapy to the radiation target<br>Drug: S-1<br>* 40-60mg/m2(according to patient's body surface area), orally twice daily every weekday concurrently with radiotherapy treatment<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>Procedure: Surgery<br>* Surgery, preferred D2 lymphadenectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR 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 telemicroscope. 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). | 6-8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| surgery complications | During hospital stay and within the first 30 days after completion of surgery. | 6-8 months | 
| Tumor down-staging | Down-staging was considered as any stage reduction between clinical and pathologic stage. | 6-8 months | 
| R0 resection rate | The surgical procedure was total or subtotal gastrectomy with recommended D2 lymphadenectomy 4-6 weeks after total neoadjuvant therapy. | 6-8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy