The Long-term Effect of D4 Lymphadenectomy for Gastric Cancer

Gastric Cancer Clinical Trial

Official title:

The Long-term Effect of D4 Lymphadenectomy for Gastric Cancer: a Multicenter, Open-label, Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02423278
• Other study ID #: 2010006
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: April 13, 2015
• Last updated: April 21, 2015
• Start date: January 2010
• Est. completion date: December 2020

Study information

• Verified date: April 2015
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: Yujie Yuan, MD
• Phone: +8615018492852
• Email: condor.yyj[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the effect of extensive lymphadenectomy procedure in treatment of gastric cancer. This study is designed as a open-label, multi-centers, randomized controlled trial. The overall survival and free disease survival are primary outcomes, with postoperative complication, hospital charges, and life quality as secondary outcomes.

Description:

Background: Gastric cancer is the second leading cause of cancer-associated death worldwide, with high incidence in China. The prognosis of advanced gastric cancer is quite poor. Although perioperative chemotherapy may help to prolong survival in cases of advanced disease, radical tumor resection remains the most effective treatment for curable gastric cancer. Nowadays, radical gastrectomy with extended (D2) lymphadenectomy has become the standard for treatment of advanced gastric cancer. However, this surgical procedure cannot achieve a radical tumor resection for most cases with advanced disease. Hence, a more extensive (D2 plus para-aortic nodal dissection, D4) lymphadenectomy along with gastrectomy has been performed in Japan and other Asian countries. A recent study by Sasako et al. indicated that a prophylactic D4 lymphadenectomy did not improve the prognosis of curable gastric cancer, but increased the blood loss and operation time compared with single D2 procedure. We reviewed our database, which had collected almost 2,000 gastric cancer cases since its establishment in 1994, and found that the D4 surgical procedure actually improved the prognosis of T4 tumor and tumor with lymph node metastasis at the second stations. To further confirm the results from our retrospective analysis, we performed a prospective study with multicenter, open-label, and randomized design in the affiliated hospitals of Sun Yat-sen University. This study would be helpful to improve the prognosis of patients with advanced gastric cancer, and find more efficient management for curable gastric cancer.

Method: This study, which started from January, 2011 and planned to close after ten years, has been approved by the ethic committee of Sun Yat-sen University, with written inform consent obtained from all enrolled subjects. Patients who had histologically proven gastric adenocarcinoma and confirmed lymph node metastasis to para-aortic nodes (<3 enlarged lymph nodes) were prospectively enrolled in this trial. A standard D2 lymphadenectomy or D4 procedure was randomly decided by a formal randomization program. The primary end point of this study was overall survival, defined as the time from randomization to death. The secondary end points were recurrence-free survival, postoperative complications, length of stay, and hospital charges. Recurrence-free survival was defined as the time from randomization to the first recurrence of cancer or death from any cause. The follow-up period would last for at least five years after the definitive operation.

Significance: This study would further confirm the efficacy of D2 plus para-aortic nodal dissection(PAND) procedure for management of advanced gastric cancer as compared with the classic D2 lymphadenectomy operation. Moreover, the therapeutic measures employed in current study may guide the future treatment of advanced gastric cancer in China.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2020
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• The informed consent has been obtained from the patient.

• With confirmed pathological diagnosis of gastric cancer and visible para-aortic lymph nodes metastasis.

• Endurable D2/D4 gastrectomy and neoadjuvant chemotherapy.

• With moderate/good ECOG health rating (PS): 0-1 score.

Exclusion Criteria:

• Pregnant woman or lactating woman.

• With confirmed distant metastasis in liver, lung, bones, or other organs.

• Intolerable operation or neoadjuvant chemotherapy.

• With severe comorbidities, such as cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and chronic renal dysfunction.

• With bad compliance or contraindication to enrollment.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Effects of Chemotherapy
• Gastric Cancer
• Stomach Neoplasms
• Surgery

Intervention

Procedure:
• Radical Gastrectomy Plus D2 Lymphadenectomy
This surgical procedure is performed by the same high-experienced surgical team as the control arm. All lymph nodes around stomach (station 1&2 LNs) must be removed to achieve a radical lymphadenectomy. Para-aortic lymph nodes should not be dissected even if a suspected lymph node metastasis is diagnosed from radiographic exams.
• Radical Gastrectomy Plus D4 Lymphadenectomy
This surgical procedure is also performed by the same high-experienced surgical team as the control arm. Lymph nodes around stomach (station 1&2 LNs) and para-aortic lymph nodes must be removed during the operation.

Drug:
• S-1+Oxaliplatin
A perioperative chemotherapy, known as SOX regimen, should be performed in each enrolled patient with three-cycle treatments followed after a pathological carcinoma diagnosis. After a radical operation (arm groups), additional five-cycle treatments of adjuvant chemotherapy (SOX regimen) would be performed, followed by follow-up program. The treatment bundles are listed as follows: S-1: 40~60mg bid,po, Day1~14 (S-1:BSA <1.25m2, 40mg bid, 1.25m2=BSA=1.5m2,50mg bid, BSA>1.5m2, 60mg bid) Oxaliplatin: 130mg/m2,iv drip for 2h,Day1

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (4)

Lead Sponsor	Collaborator
First Affiliated Hospital, Sun Yat-Sen University	Second Affiliated Hospital, Sun Yat-Sen University, Sixth Affiliated Hospital, Sun Yat-sen University, Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		five years after surgery	Yes
Primary	Relapse-free Survival		five years after surgery	Yes
Secondary	Early complications	Rate of early postoperative events, such as anastomotic leak, intra-abdominal hemorrhage, adhesive intestinal obstruction and surgical site infection, in each arm.	within the first 30 days after surgery	No
Secondary	Perioperative mortality		within the first 30 days after surgery	Yes
Secondary	Life quality measured by HRQOL score	a questionnaire form would be sent to each enrolled patients after surgery.	five years after surgery	No
Secondary	Length of Hospital stay	The duration between admission and final discharge from hospital. An average of 4 weeks is expected.	an expected average of 4 weeks after admission	No