Laparoscopic vs. Open Distal Gastrectomy After Neoadjuvant Chemotherapy

A Multicenter Prospective Phase II Comparative Study of Laparoscopic Versus Open Distal Gastrectomy After Neoadjuvant Chemotherapy for the Treatment of Locally Advanced Gastric Cancer Patients

The study was designed as single-country, multi-center, open-labelled, randomized (1:1), phase II trial.

238 patients with medically and technically operable advanced gastric adenocarcinoma in middle or distal 1/3 of stomach are enrolled and randomly assigned to laparoscopic gastrectomy group and open gastrectomy group. 4 cycles of mFLOT chemotherapy will be conducted before and after gastrectomy.

The primary objective of this study is comparison of D2 lymph node dissection compliance rate between open surgery group and laparoscopic surgery group after neoadjuvant chemotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Stomach Neoplasm
• Intervention / Treatment: Procedure: Laparoscopic versus open distal gastrectomy

Detailed Description

The effect of neoadjuvant chemotherapy on locally advanced gastric cancer was confirmed from a prospective clinical trial. Oncologic safety and excellence of the laparoscopic gastrectomy surgery was recently established for locally advanced gastric cancer.

However, neither technical nor oncologic stability was established for laparoscopic gastrectomy surgery after neoadjuvant chemotherapy. Anticipated benefits from laparoscopic gastrectomy surgery after neoadjuvant chemotherapy are as follows: 1) Reduced postoperative complications; 2) Reduced intra- or postoperative transfusion and patient's pain after surgery; 3) Enhance postoperative recovery (shortened hospitalization duration); 4) Facilitate completion rate of adjuvant chemotherapy.

The study was designed as single-country, multi-center, open-labelled, randomized (1:1), phase II trial.

238 patients with medically and technically operable advanced gastric adenocarcinoma in middle or distal 1/3 of stomach are enrolled and randomly assigned to laparoscopic gastrectomy group and open gastrectomy group. 4 cycles of mFLOT chemotherapy will be conducted before and after gastrectomy.

The primary objective of this study is comparison of D2 lymph node dissection compliance rate between open surgery group and laparoscopic surgery group after neoadjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 238
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Young-Kyu Park, MD; Phone Number: +82-10-7173-1196; Email: parkyk@jnu.ac.kr
• Study Contact Backup: Name: Joong-Min Park, MD; Email: jmpark@cau.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who voluntarily expressed their consent to participate in this trial by signing a written 'Subject Consent Form.'
2. Patients whose gastric adenocarcinoma located in the middle or lower part of the stomach is histologically confirmed and deemed possible to perform a radical distal gastrectomy surgery.
3. Patients who come under T2/N(+)M0, T3~4a/N(- or +) M0 according to the 8th edition of the TNM classification.

Exclusion Criteria:

• Methodologies

  1. Patients less than 20 years old or older than 80 years old
  2. Eastern Cooperative Oncology Group(ECOG) ≥ 2
  3. Patients with a surgery experience due to a neoplasm in the stomach.
  4. Patients with complications due to gastric cancer (acute hemorrhage, gastric outlet obstruction or perforation)
  5. Patients with distant metastases (M1) including distant lymph nodes (Retropancreatic, para-aortic, periportal, retroperitoneal, or mesenteric lymph nodes)
  6. Patients without distant metastases but who are, according to a surgeon's judgment, unqualified for radical gastrectomy because of invasions to adjacent organs (T4b).
  7. In the case of localized conglomerated metastatic lymph nodes
  8. Patients who received surgery or radiation therapy for a primary cancer developed in another organ or those with active/synchronous double cancer in recent 5 years.
  9. Patients who participated in another clinical trial or was administered with a different investigational drug in 30 days prior to randomization.
  10. Patients who had any of the following in 6 months before the trial recruitment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass surgery, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
  11. Patients with a previous experience of uncontrolled seizure, central nervous system or psychological disorders whose conditions are clinically significant to the extent that they are unable to express consent to participate in the trial and oral drug administration is not possible.
  12. Patients with uncontrolled active infection or sepsis.
  13. Patients who had deep vein thrombosis in recent 4 weeks before the beginning of the trial recruitment.
  14. Patients with serious acute or chronic disease that can degrade the patient's ability to participate in the trial or impede the interpretation of the trial results.

  15. Pregnant or breast-feeding patients. Fertile female patients who are positive in pregnancy test.

      Drug Administration for Neoadjuvant Chemotherapy

  16. Inadequate functions of marrow or organs:

      I. Absolute Neutrophil Count (ANC) < 1.5 x 109/L II. Platelet (PLT) < 100 x 109/L III. Hemoglobin (Hb) ≤ 9 g/dL IV. AST> 2.5 x ULN, ALT> 2.5 x ULN V. ALP > 2.5 x ULN VI. Total Bilirubin (T. Bil) > 1.5 x ULN VII. Serum creatinine (Cr) > 1.5 x ULN

  17. Patients who have peripheral neuropathy with clinical signs of Grade≥2 (NCI CTCAE v4.03) or with absence of deep tension reflex (DTR).
  18. Patients with hypersensitivity history of the investigational drug (5-FU, Oxaliplatin, Docetaxel).
  19. Patients who are on treatment with warfarin or coumarin anticoagulants.
  20. Patients who are on immunosuppressive therapy.
  21. Patients who are receiving co-medication with Cytochrome P450 2A6 inducer, inhibitor, and substrate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Laparoscopic distal gastrectomy; Laparoscopic distal gastrectomy after neoadjuvant chemotherapy for the treatment of locally advanced gastric cancer patients	Procedure: Laparoscopic versus open distal gastrectomy; Laparoscopic versus open distal gastrectomy after neoadjuvant chemotherapy for locally advanced gastric cancer
ACTIVE_COMPARATOR: Open distal gastrectomy; Open distal gastrectomy after neoadjuvant chemotherapy for the treatment of locally advanced gastric cancer patients	Procedure: Laparoscopic versus open distal gastrectomy; Laparoscopic versus open distal gastrectomy after neoadjuvant chemotherapy for locally advanced gastric cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of harvested lymph nodes in D2 lymph node dissection	number of lymph nodes, pathologically proven after surgery	2 weeks after operation when the pathologic report is available

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year progression free survival	PFS is defined as time from the point of randomization to objective tumor progression or relapse, or to death according to RECIST 1.1.	3 years after randomization
3 year relapse free survival	RFS is defined as time from the point of randomization to tumor relapse or death	3 years after randomization
Comparison of postoperative morbidity and mortality	Defined as the incidence of complications within 30 days after surgery, death rate within 90 days. Classification and severity of the complications shall be based on that of KLASS-02-RCT.	90 days after operation
Curative resection rate	Defined as a case where complete removal of all tumors were confirmed through gross or microscopic examination; negative resection margin was obtained; and, D2 lymph node dissection was performed.	2 weeks after operation when the pathologic report is available
Conversion to open surgery	Defined as a case which the laparoscopic surgery was converted to an open surgery in the operation time, because of reasons including combined organ resection due to adjacent organ invasion, severe intra-abdominal adhesion, or serious intraoperative bleeding.	1 day

Collaborators and Investigators

• Sponsor: Chonnam National University Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2021
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): December 1, 2026

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (ACTUAL): December 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: H2020-0407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No