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

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03680261
• Other study ID #: ZSGC-004
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 1, 2018
• Est. completion date: September 30, 2023

Study information

• Verified date: September 2018
• Source: Shanghai Zhongshan Hospital
• Contact: Xuefei Wang, MD, PhD
• Phone: 86-13917270428
• Email: wang.xuefei[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 556
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Radiation:
• chemoradiotherapy
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.

Drug:
• chemotherapy
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.

Locations

Country	Name	City	State
China	ZhongShan hospital FuDan university	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (18)

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Dicken BJ, Graham K, Hamilton SM, Andrews S, Lai R, Listgarten J, Jhangri GS, Saunders LD, Damaraju S, Cass C. Lymphovascular invasion is associated with poor survival in gastric cancer: an application of gene-expression and tissue array techniques. Ann Surg. 2006 Jan;243(1):64-73. — View Citation

Dikken JL, van Sandick JW, Maurits Swellengrebel HA, Lind PA, Putter H, Jansen EP, Boot H, van Grieken NC, van de Velde CJ, Verheij M, Cats A. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer. 2011 Aug 2;11:329. doi: 10.1186/1471-2407-11-329. — View Citation

Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002 Oct 17;347(16):1233-41. — View Citation

Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. doi: 10.1200/JCO.2011.39.1953. Epub 2011 Dec 19. — View Citation

Lee JH, Kim MG, Jung MS, Kwon SJ. Prognostic significance of lymphovascular invasion in node-negative gastric cancer. World J Surg. 2015 Mar;39(3):732-9. doi: 10.1007/s00268-014-2846-y. — View Citation

Li P, He HQ, Zhu CM, Ling YH, Hu WM, Zhang XK, Luo RZ, Yun JP, Xie D, Li YF, Cai MY. The prognostic significance of lymphovascular invasion in patients with resectable gastric cancer: a large retrospective study from Southern China. BMC Cancer. 2015 May 7;15:370. doi: 10.1186/s12885-015-1370-2. — View Citation

Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. — View Citation

Mamon HJ, Tepper JE. Combination chemoradiation therapy: the whole is more than the sum of the parts. J Clin Oncol. 2014 Feb 10;32(5):367-9. doi: 10.1200/JCO.2013.54.3108. Epub 2014 Jan 13. — View Citation

Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. doi: 10.1016/S1470-2045(14)70473-5. Epub 2014 Oct 15. — View Citation

Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III Trial to Compare Adjuvant Chemotherapy With Capecitabine and Cisplatin Versus Concurrent Chemoradiotherapy in Gastric Cancer: Final Report of the Adjuvant Chemoradiotherapy in Stomach Tumors Trial, Including Survival and Subset Analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. doi: 10.1200/JCO.2014.58.3930. Epub 2015 Jan 5. — View Citation

Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. — View Citation

Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. doi: 10.1200/JCO.2011.36.7136. Epub 2012 May 14. — View Citation

Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010 May;11(5):439-49. doi: 10.1016/S1470-2045(10)70070-X. Epub 2010 Apr 19. — View Citation

Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000 Mar 1;92(5):388-96. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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