Preoperative Concurrent Chemoradiotherapy for Locally Advanced Gastroesophageal Junction or Upper Gastric Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
Preoperative chemoradiotherapy(CRT) had been introduced in the comprehensive treatment of gastroesophageal junction and upper gastric cancers in the decade.According to some researches,CRT had shown its good curative effects in local control and prolonged overall survival.However,the optimization scheme for CRT and its influence to surgery remains controversial.Meanwhile,there were many design flaws in the past few research,such as the lack of adjuvant chemotherapy,the insufficiency in lymphnodes dissection.We decided to carry out the trial,eliminating all the bias as far as we can,to illustrate the efficacy and safety of CRT.

Official Title
-----------------
Phase Ⅱ/Ⅲ Study of Preoperative Concurrent Chemoradiotherapy for Locally Advanced Gastroesophageal Junction or Upper Gastric Adenocarcinoma

Conditions
-----------------
Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
-----------------
* Radiation: Preoperative concurrent chemoradiotherapy
* Procedure: Radical D2 total gastrectomy
* Drug: Adjuvant chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven adenocarcinoma of the gastroesophageal junction. Clinical stage diagnosed by endoscopic ultrasound(EUS) or computed tomography(CT) as T3-4NxM0 tumors,according to American Joint Committee on Cancer (AJCC) 7th edition. Eastern Cooperative Oncology Group (ECOG) performance status≤2. Informed consent obtained. Exclusion Criteria: Combined with other malignant tumors. Eastern Cooperative Oncology Group (ECOG) performance status>2. Combined with severe organ dysfunction. Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: CCRT group<br>The patient in CCRT group will receive the preoperative concurrent chemoradiotherapy for 5 weeks and sequential radical D2 total gastrectomy and postoperative adjuvant chemotherapy of 6 cycles. | Radiation: Preoperative concurrent chemoradiotherapy<br>* The patients will receive radiotherapy in the total amount of 50Gy(25 fractions) preoperatively,concurrently combined with chemotherapy,which consist of oxaliplatin 40mg/m2 administrated on days 1,8,15,22,29 and S-1® 30mg/m2 twice per day on days 1 to 5 per week.<br>* Other names: S-1®;Procedure: Radical D2 total gastrectomy<br>* Within 5-6 weeks after the completion of neoadjuvant therapy,the patients in CCRT group will receive the radical total gastrectomy with D2 lymphadenectomy,and patients in the CT group will receive the surgery right after randomization.<br>Drug: Adjuvant chemotherapy<br>* Within 2 months after surgery,the patients will receive chemotherapy for 6 to 8 cycles ,consist of oxaliplatin 130mg/m2 administrated on day1 and S-1® 40-60mg twice per day on days 1 to 14 per 3 weeks.The S-1® dosage depends on the patient BSA(BSA<1.25m2 40mg,1.25 m2≤BSA≤1.5 m2 50mg ,BSA>1.5 m2 60mg). Patients in the CCRT group will receive 6 cycles of chemotherapy and patients in the CT group will receive 8 cycles of chemotherapy.<br>* Other names: S-1®;|
| Active Comparator: CT group<br>The patient in CT group will receive radical D2 total gastrectomy and postoperative adjuvant chemotherapy of 8 cycles. | Procedure: Radical D2 total gastrectomy<br>* Within 5-6 weeks after the completion of neoadjuvant therapy,the patients in CCRT group will receive the radical total gastrectomy with D2 lymphadenectomy,and patients in the CT group will receive the surgery right after randomization.<br>Drug: Adjuvant chemotherapy<br>* Within 2 months after surgery,the patients will receive chemotherapy for 6 to 8 cycles ,consist of oxaliplatin 130mg/m2 administrated on day1 and S-1® 40-60mg twice per day on days 1 to 14 per 3 weeks.The S-1® dosage depends on the patient BSA(BSA<1.25m2 40mg,1.25 m2≤BSA≤1.5 m2 50mg ,BSA>1.5 m2 60mg). Patients in the CCRT group will receive 6 cycles of chemotherapy and patients in the CT group will receive 8 cycles of chemotherapy.<br>* Other names: S-1®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The patient's survival time and recurrence time | 3-year overall survival 1-year and 3-year recurrence free survival | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with complications | the morbidity and mortality rates within 30 days after the day of operation | Within 30 days after the day of operation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preoperative concurrent chemoradiotherapy, Neoadjuvant chemoradiotherapy, Gastroesophageal junction adenocarcinoma