Transarterial Neoadjuvant Chemotherapy vs.Traditional Intravenous Chemotherapy For Locally Advanced Gastric Cancer With SOX+PD-1 (TACTIC)

A Multicenter, Randomized, Controlled Study of S-1 Combined With Oxaliplatin by Arterial Infusion Plus PD-1 Antibody Versus Conventional SOX Chemotherapy Plus PD-1 Antibody for Locally Advanced Gastric Cancer

SOX regimen, consisting of oral S-1 and intravenous oxaliplatin, is the preferred regimen for perioperative chemotherapy for gastric cancer. The goal of this clinical trial is to compare the efficacy and safety between S-1 combined with oxaliplatin by arterial infusion, as neoadjuvant chemotherapy, and conventional SOX regimen, in locally advanced gastric cancer. The main question it aims to answer is: whether arterially infused oxaliplatin plus S-1 has the potential to be a better neoadjuvant option for patients with locally advanced gastric cancer.

Participants will be randomised, and receive:

• 3 cycles of conventional SOX chemotherapy plus PD-1 antibody or arterial infused oxaliplatin plus S-1 and PD-1 antibody, as neoadjuvant chemotherapy;
• Adequate gastric resection along with D2 lymph node dissection;
• 3 cycles adjuvant chemotherapy using SOX regimen plus PD-1 antibody.
• Administration of S-1 regularly till 1 year after surgery.

Researchers will compare Major pathological response rate (MPR) ，pathologic complete response rate（pCR）,the 2-year overall survival (OS) rates, 2-year disease free survival (DFS), R0 resection rates, and adverse events, to see if the modified perioperative chemotherapy improve the prognosis of patients with locally advanced gastric cancer.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Gastric Carcinoma
• Intervention / Treatment: Drug: Oxaliplatin by arterial infusion plus S-1; Procedure: gastrectomy plus D2 lymph node dissection; Drug: SOX neoadjuvant; Drug: Sintilimab neoadjuvant; Drug: SOX adjuvant, Sequential S-1; Drug: Sintilimab adjuvant

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shenbin XU, Doctor; Phone Number: 86-15057315353; Email: shenbin_xu@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Gastrointestinal Department of Second Affiliated Hospital of Zhejiang University
      • Contact: Shenbin XU, Doctor; Phone Number: 86-15057315353; Email: shenbin_xu@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group(ECOG) score 0-1
• Ambulatory males or females, aged 18-75 years
• Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II or III)
• Locally advanced gastric carcinoma (cT3N2-3M0, cT4aN1-3M0, cT4bNanyM0, American Joint Committee on Cancer (AJCC) TNM staging system 8th edition)
• Life expectancy more than 3 months
• Give written informed consent, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• Normal hepatic, renal, and bone marrow function (ALT/AST<2.5 fold of upper limit value;Tbil<1.5mg/dl, Cr<1.5 fold of upper limit value; White Blood Cell count≥3 × 10^9/L, ANC ≥ 1.5 × 10^9/L,PLT≥ 80 × 10^9/L,Hb ≥ 90 g/L).

Exclusion Criteria:

• Patients can not bear surgical procedure.
• Pregnant or lactating women.
• HER2 overexpression(+++) confirmed by immunohistochemistry.
• Previous cytotoxic chemotherapy, radiotherapy or immunotherapy.
• History of another malignancy within the last five years.
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the Investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.
• Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication or myocardial infarction within the last 12 months.
• History of dysphagia, complete or partial gastrointestinal obstruction, active gastrointestinal bleeding and gastrointestinal perforation;
• Organ allografts requiring immunosuppressive therapy.
• Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease.
• Moderate or severe renal impairment: serum creatinine > 1.5 x upper limit of normal (ULN).
• Hypersensitivity to any drug of the study regimen.
• With abdominal cavity implantation metastasis or distant metastasis.
• Unwilling or unable to comply with the protocol for the duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arterial infusion group; 3 cycles of neoadjuvant chemotherapy: Oxaliplatin arterial infusion+S-1; 3 cycles of immunotherapy: sintilimab; surgery and 3 cycles of adjuvant chemotherapy using SOX regimen plus sintilimab.; S-1 administration till 1 year after surgery	Drug: Oxaliplatin by arterial infusion plus S-1; 3 cycles oxaliplatin by arterial infusion plus S-1 every 21 days as neoadjuvant chemotherapy.; Procedure: gastrectomy plus D2 lymph node dissection; All patients, whose lesions are resectable and medically operable after 3 cycles neoadjuvant chemotherapy, will receive gastrectomy plus D2 lymph node dissection.; Drug: Sintilimab neoadjuvant; 3 cycles of neoadjuvant immunotherapy every 21 days.; Drug: SOX adjuvant, Sequential S-1; 3 cycles of SOX adjuvant chemotherapy every 21 days after surgery in both groups. Sequential S-1 chemotherapy every 21 days till 1 year postoperation.; Drug: Sintilimab adjuvant; 3 cycles of adjuvant immunotherapy every 21 days.
Active Comparator: SOX group; 3 cycles of neoadjuvant chemotherapy: SOX regimen; 3 cycles of immunotherapy: sintilimab; surgery and 3 cycles of adjuvant chemotherapy using SOX regimen plus sintilimab.; S-1 administration till 1 year after surgery	Procedure: gastrectomy plus D2 lymph node dissection; All patients, whose lesions are resectable and medically operable after 3 cycles neoadjuvant chemotherapy, will receive gastrectomy plus D2 lymph node dissection.; Drug: SOX neoadjuvant; 3 cycles of SOX neoadjuvant chemotherapy every 21 days.; Drug: Sintilimab neoadjuvant; 3 cycles of neoadjuvant immunotherapy every 21 days.; Drug: SOX adjuvant, Sequential S-1; 3 cycles of SOX adjuvant chemotherapy every 21 days after surgery in both groups. Sequential S-1 chemotherapy every 21 days till 1 year postoperation.; Drug: Sintilimab adjuvant; 3 cycles of adjuvant immunotherapy every 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response rate	The percentage of people who has less than or equal to 10% residual viable tumor after neoadjuvant therapy.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	The proportion of patients with margin-free resection	6 months
2-year Disease Free Rate	The percentage of individuals in this study who are free of the signs and symptoms of gastric cancer at 2 years after treatment	2 years
2-year Overall Survival Rate	The percentage of individuals in this study who are alive two years after their diagnosis or the start of treatment.	2 years
pathological Complete Response rate	The percentage of people with complete disappearance of all invasive carcinoma cells.	6 months

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 19, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; gastric cancer; neoadjuvant therapy; arterial infusion
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: ZEWC_GC_I002

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