Clinical trial NCT03680261: Enriched-CRT 2017: Advanced Gastric Cancer With LN+ and LVI+, Chemotherapy vs. Chemoradiotherapy
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Gastric Cancer
Keywords: Gastric Cancer
Chemoradiotherapy
Chemotherapy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2018-09-21
Enrollment: 556
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 3-year Overall Survival
timeFrame: 3-year
Secondary outcomes:
measure: 3-year Disease Free Survival
timeFrame: 3-year
measure: Adverse effect (Safety and Tolerability)
timeFrame: 30 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: ZhongShan hospital FuDan university
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xuefei Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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