Standard Versus Super-extended Lymphadenectomy After Neo-adjuvant Chemotherapy for Gastric Cancer

NCT ID: NCT03961373

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 539 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-05
• Study Completion Date: 2028-11-01

Brief Summary

In this study the patients with histological evidence of adenocarcinoma of the stomach will be screened and, if eligible, submitted to neo-adjuvant chemotherapy (NAC). After conclusions of NAC and obtaining informed consent, they will be registered and randomized to receive surgical D2 vs. D2plus lymphadenectomy.

Detailed Description

This is a prospective multi-centre phase III, two-group, randomized and controlled trial designed to prove superiority of the experimental treatment arm (neo-adjuvant chemotherapy and super-extended lymphadenectomy).

The trial population consists of patients who have histologically confirmed adenocarcinoma of the stomach with locally advanced primary tumour and no evidence of distant metastases (stage IIA-IIIC gastric cancer). The lymph node clinical metastases, before neo-adjuvant chemotherapy, must be limited to the first and second compartments (stations 1-12).

STANDARD GROUP: Neoadjuvant chemotherapy + surgical gastrectomy with D2 lymphadenectomy.

Patients who are assigned to neoadjuvant chemotherapy+ surgical D2 treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2-lymph node dissection is required with specific information about lymph node stations.

EXPERIMENTAL GROUP: Neoadjuvant chemotherapy + surgical gastrectomy with D2plus lymphadenectomy.

Patients who are assigned to neoadjuvant chemotherapy + surgical D2plus extended lymphadenectomy treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2 lymph node dissection plus resection of stations 8p, 12b/p, 13, 14v, 16a2/b1 is required with specific information about lymph node stations.

In both groups, surgical treatment should be performed within 4-6 weeks after the end of the last cycle of NAC.

The primary objective of this study is to compare overall and cancer-related survival between D2 and D2+ lymphadenectomy following neo-adjuvant chemotherapy for resectable gastric cancer.

In addition, response to chemotherapy, resection rate, quality of life, complications attributable to surgical intervention / side effects of chemotherapy and the duration of hospitalization will be evaluated.

Sample size estimation was performed, to detect the minimum number of patients to be recruited in each arm. A two-sided log rank test with an overall sample size of 539 subjects, of which 270 are in group 1 and 269 are in group 2.

Data will be analyzed using SPSS software. Level of significance will be defined as 5%.

The trial will be open for recruitment from October 2018 to September 2023.

Conditions

Locally Advanced Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Group

Neoadjuvant chemotherapy + surgical gastrectomy with D2 lymphadenectomy

Group Type: ACTIVE_COMPARATOR

Gastrectomy with D2 lymphadenectomy

Intervention Type: PROCEDURE

Patients who are assigned to the neoadjuvant chemotherapy+ surgical D2 treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2-lymph node dissection is required with specific information about lymph node stations.

Experimental Group

Neoadjuvant chemotherapy + surgical gastrectomy with D2plus lymphadenectomy

Group Type: EXPERIMENTAL

Gastrectomy with D2plus lymphadenectomy

Intervention Type: PROCEDURE

Patients who are assigned to the neoadjuvant chemotherapy + surgical D2+ extended lymphadenectomy treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2+ lymph node dissection plus resection of stations 8p, 12p, 13, 14v, 16a2/b1 is required with specific information about lymph node stations.

Interventions

Gastrectomy with D2 lymphadenectomy

Patients who are assigned to the neoadjuvant chemotherapy+ surgical D2 treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2-lymph node dissection is required with specific information about lymph node stations.

Intervention Type: PROCEDURE

Gastrectomy with D2plus lymphadenectomy

Patients who are assigned to the neoadjuvant chemotherapy + surgical D2+ extended lymphadenectomy treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2+ lymph node dissection plus resection of stations 8p, 12p, 13, 14v, 16a2/b1 is required with specific information about lymph node stations.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age equal or greater than 18 years
• IIA-IIIC histologically proven primary gastric adenocarcinoma, before the treatment with NAC. Not including gastro-oesophageal junction/cardia carcinoma but only Siewert 3, without any previous treatment (surgery and / or chemotherapy) for this diagnosis
• Lack in CT scan of following:

1. Mediastinal lymph nodes

2. Lung metastases

3. Peritoneal metastases

4. Liver metastases

5. Pleural effusion, ascites

6. Metastases to para-aortic lymph nodes No 16a2/b1

7. Metastases to lymph nodes located in the "posterior" area (8p, 12 b/p, 13)

8. Extra-regional lymph node metastases

• ECOG performance status ≤ 2
• No prior radio- or chemotherapy conflicting with the treatment of gastric cancer
• No oesophageal invasion, or invasion <=3cm
• Negative peritoneal washing cytology findings and no peritoneal metastases in staging laparoscopy
• No gastric stump cancer
• No signs of cervical and subclavear lymph nodes or distal metastases
• Patient's consent form obtained, signed and dated before beginning specific protocol procedures
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Exclusion Criteria

• Contraindications for any sort of appropriate chemotherapy according to local standards
• Linitis plastica
• Second uncontrolled malignant tumour (synchronous or metachronous (last 5 years) other than Cis or mucosal cancer
• Neoplasms involving the esophago-gastric junction (Siewert types I and II)
• Expected unresectability after neo-adjuvant treatment or progression in metastases
• Emergency surgery due to bleeding or perforation
• Uncontrolled infections
• Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
• Pregnant or lactating women
• Significant neurologic or psychiatric disorders
• Severe cardiac illness (NYHA class IV)
• Under treatment of systemic steroids
• Participation in any other clinical trial that might interfere with the results of this trial
• Lack of compliance
• Inability to fill in questionnaires (insufficient command of language, dementia, lack of time)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Siena

OTHER

Sponsor Role: lead

Responsible Party

Franco Roviello

Full Professor, Clinical Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Franco Roviello

Role: PRINCIPAL_INVESTIGATOR

University of Siena

Locations

General and Surgical Oncology Department, University of Siena

Siena, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Daniele Marrelli

Role: CONTACT

daniele.marrelli@unisi.it

+39577585157

Facility Contacts

Daniele Marrelli

Role: primary

daniele.marrelli@unisi.it

+39577585157

Other Identifiers

Neo-D2plus trial

Identifier Type: -

Identifier Source: org_study_id