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

Official title

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

Overview

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.

Interventions

• Drug Oxaliplatin by arterial infusion plus S-1
  3 cycles oxaliplatin by arterial infusion plus S-1 every 21 days as neoadjuvant chemotherapy.
• Drug SOX neoadjuvant
  3 cycles of SOX neoadjuvant chemotherapy every 21 days.
• Drug Sintilimab neoadjuvant
  3 cycles of neoadjuvant immunotherapy every 21 days.
• 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 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.

Primary outcome measures

• Major Pathological Response rate [Time frame: 6 months]

Secondary outcome measures (4)

• R0 resection rate [Time frame: 6 months]
• 2-year Disease Free Rate [Time frame: 2 years]
• 2-year Overall Survival Rate [Time frame: 2 years]
• pathological Complete Response rate [Time frame: 6 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Gastrointestinal Department of Second Affiliated Hospital of Zhejiang University — Hangzhou

Identifiers

NCT: NCT05593458 · ZEWC_GC_I002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗