Enriched-CRT 2017: Advanced Gastric Cancer With LN+ and LVI+, Chemotherapy vs. Chemoradiotherapy

Study Overview
=================
Brief Summary
-----------------
This Enriched-CRT 2017 trial is a prospective, multicenter trial for adjuvant chemoradiotherapy (CRT) and chemotherapy (CT) in radical resected advanced gastric cancer (GC) patients with lymph node metastasis (LN+) and lymphovascular Invasion (LVI+). The primary purpose of this study is to evaluate the 3-year overall survival (OS) of enrolled patients receiving adjuvant chemoradiotherapy compared with those receiving adjuvant chemotherapy. The second purpose is to evaluate 3-year disease free survival (DFS) and determine the safety of CRT compared with CT in the patients enrolled in this study.

Detailed Description
-----------------
Gastric cancer is an important health problem, being the fourth most common cancer and the third leading cause of cancer-related death worldwide. Age standardized mortality rates for gastric cancer are 14.3 per 100 000 in men and 6.9 per 100 000 in women. More than 679 000 new cases and 498,000 deaths occur every year in China. Local recurrence is considered as the most common way of recurrence for advanced gastric cancer, as well as an important factor for poor prognosis. Radiotherapy is a widely used technique in Western countries, and has been identified to have a significant role in decreasing local recurrence rate in breast cancer, and colon rectal cancer. At this moment, several randomized controlled trials have been conducted to identify the role of radiotherapy in advanced gastric cancer. Although the results from Europe (INT-0116), Dutch (CRITICS), and Korea (ARTIST) did not find that radiotherapy could improve the overall survival of enrolled patients, the sub-group analyses demonstrated that radiotherapy could improve the disease-free survival in patients with lymph node metastasis. We also found that adjuvant chemoradiotherapy could improve the survival of patients with lymph node metastasis or lymphovascular Invasion based on a large cohort study from National Cancer Database. Therefore, our hypothesis is that advanced gastric cancer patients with lymph node metastasis or lymphovascular invasion are the group entity that could benefit from radiotherapy. At present, a new clinical trial (ARTIST II), aiming at advanced gastric cancer with positive lymph node metastasis, has been launched. China is one of the countries with the highest incidence of gastric cancer, sand nearly 80% of patients are diagnosed with advanced stage. So it's necessary to conduct the clinical research on this issue. This Enriched-CRT 2017 trial is a prospective, multicenter trial for adjuvant chemoradiotherapy (CRT) and chemotherapy (CT) in radical resected advanced gastric cancer patients with lymph node metastasis and lymphovascular Invasion. The primary purpose of this study is to evaluate the 3-year overall survival (OS), and the second purpose is to evaluate 3-year disease free survival (DFS) and determine the safety of CRT compared with CT in the patients enrolled in this study.

Official Title
-----------------
Phase III Multicenter Randomized Controlled Trial of Adjuvant Chemoradiotherapy vs Chemotherapy for Radical Resected Advanced Gastric Carcinoma Concurrent With Lymph Node Metastasis and Lymphovascular Invasion

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Radiation: chemoradiotherapy
* Drug: chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Aged 18-75 years； 2. Primary lesion is pathologically diagnosed as gastric adenocarcinoma (including Esophagogastric Junction adenocarcinoma), such as papillary adenocarcinoma, tubular adenocarcinoma, mucinous adenocarcinoma, poorly cohesive carcinoma (including signet ring cell carcinoma and other variants), and mixed adenocarcinoma; 3. Received radical resection: R0 gastrectomy with D1/D2 lymphadenectomy (at least 15 lymph nodes were examined); 4. Pathological stage pT2-4aN1-3M0 (According to American Joint Committee on Cancer (AJCC)-7th Tumor-Node-Metastasis (TNM) staging system), and with lymphovascular invasion, (LVI+); 5. No evidence of distant metastases was observed by perioperative imaging; 6. Postoperative performance status (ECOG, Eastern Cooperative Oncology Group) of 0-2; 7. No prior treatment of chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.; 8. Adequate hematological function: Hemoglobin (Hb) ≥100g/L, Neutrophil count (ANC) ≥1.5×109/L, Platelet count (PLC) ≥100×109/L; 9. Adequate liver function: ALT、AST ≤2.5x upper limit of normal (ULN), Alkaline phosphatase (ALP) ≤2.5x ULN, Serum total bilirubin (TBIL) <1.5x ULN, Serum albumin(Alb) ≥30g/L; 10. Adequate renal function: Serum creatinine ≤1.5mg/dl; 11. Be able of oral feeding; 12. Written informed consent. Exclusion Criteria: 1. Synchronous or metachronous (within 5 years) malignancies; 2. Body temperature ≥ 38℃ or infectious disease with a systemic therapy indicated; 3. Severe neurological or mental disease, including seizures or dementia, which may interfere compliance and sign of consent inform. 4. Severe heart disease, including unstable angina pectoris, New York Heart Association (NYHA) class II or more advanced heart failure, severe arrhythmia despite medicinal treatment, or history of myocardial infarction within 12 months; 5. Severe respiratory disease; 6. Moderate or severe renal dysfunction: Creatinine clearance rate (CCR) ≤50 ml/min, or Serum creatinine >ULN ; 7. Upper gastrointestinal tract obstruction, physiological dysfunction, or malabsorption syndrome, which affect the absorption of oral drugs; 8. Peripheral nervous disease (NCI CTC version> 1.0 grade), except for patients with ony disappeared deep tendinous reflect (DTR); 9. Women during pregnancy or breast-feeding; 10. Fertile women with a positive pregnancy test, or no pregnancy test; postmenopausal within 12 months; 11. Fertile men or women who refuse to use contraception during the study period; 12. Patients are participating or have participated in another clinical trial (within 6 months); 13. Continuous systemic steroid therapy within 1 month (except for topical use), or received organ transplantation that needs immunosuppressive agent; 14. Dihydropyrimidine dehydrogenase (DPD) deficiency; 15. Allergy to platinum compound, or any component of drugs used in the study.

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: Adjuvant chemoradiotherapy group<br>Adjuvant chemoradiotherapy (1 cycle CT: Oxaliplatin plus capecitabine (Xelox) or S-1 plus oxaliplatin (SOX), Q21d×1, Followed by RT: 45 Gray (Gy), 5d/week×5 with capecitabine or S1, Followed by 3 cycles CT: Xelox or SOX, Q21d×3) for patients enrolled in this group. | Radiation: chemoradiotherapy<br>* CRT (1 cycle CT: Xelox or SOX, Q21d×1, Followed by RT: 45 Gray (Gy), 5d/week×5 with capecitabine or S1, Followed by 3 cycles CT: Xelox or SOX, Q21d×3) will be applied to radical resected advanced gastric cancer patients with lymph node metastasis and lymphovascular Invasion.<br>* Other names: Study group (CRT);|
| Active Comparator: Adjuvant chemotherapy group<br>Adjuvant chemotherapy (6 cycles CT: Xelox or SOX, Q21d×3) for patients enrolled in this group. | Drug: chemotherapy<br>* CT (6 cycles CT: Xelox or SOX, Q21d×3) will be applied to radical resected advanced gastric cancer patients with lymph node metastasis and lymphovascular Invasion.<br>* Other names: Control group (CT);|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Overall Survival | 3-year Overall survival (OS) was defined as the time from the date of enrollment to the date of death or last visit. | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Disease Free Survival | 3-year Disease Free Survival (DFS) was defined as time from the date of enrollment to the date of recurrence or last visit. | 3-year | 
| Adverse effect (Safety and Tolerability) | The evaluation of adverse effect is based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gastric Cancer, Chemoradiotherapy, Chemotherapy