Clinical trial NCT02423278: The Long-term Effect of D4 Lymphadenectomy for Gastric Cancer
Official title: The Long-term Effect of D4 Lymphadenectomy for Gastric Cancer: a Multicenter, Open-label, Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Gastric Cancer
Surgery
Effects of Chemotherapy
Keywords: gastrectomy
lymphadenectomy
gastric cancer
adjuvant chemotherapy
overall survival
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, Sun Yat-Sen University
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Sixth Affiliated Hospital, Sun Yat-sen University
First posted: 2015-04-22
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: five years after surgery
measure: Relapse-free Survival
timeFrame: five years after surgery
Secondary outcomes:
measure: Early complications
timeFrame: within the first 30 days after surgery
measure: Perioperative mortality
timeFrame: within the first 30 days after surgery
measure: Life quality measured by HRQOL score
timeFrame: five years after surgery
measure: Length of Hospital stay
timeFrame: an expected average of 4 weeks after admission
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Yulong He, MD
role: STUDY_DIRECTOR
References: