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

NCT05593458 | Recruiting Phase 3

• 1 other identifier: ZEWC_GC_I002
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Locally Advanced Gastric Carcinoma

Keywords

gastric cancer; arterial infusion; neoadjuvant therapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• R0 resection rate

  6 months

• 2-year Disease Free Rate

  2 years

• 2-year Overall Survival Rate

  2 years

• pathological Complete Response rate

  6 months

Study Arms (2)

Arterial infusion group

EXPERIMENTAL

1. 3 cycles of neoadjuvant chemotherapy: Oxaliplatin arterial infusion+S-1 2. 3 cycles of immunotherapy: sintilimab 3. surgery and 3 cycles of adjuvant chemotherapy using SOX regimen plus sintilimab. 4. S-1 administration till 1 year after surgery

Drug: Oxaliplatin by arterial infusion plus S-1; Drug: Sintilimab neoadjuvant; Procedure: gastrectomy plus D2 lymph node dissection; Drug: SOX adjuvant, Sequential S-1; Drug: Sintilimab adjuvant

SOX group

ACTIVE COMPARATOR

1. 3 cycles of neoadjuvant chemotherapy: SOX regimen 2. 3 cycles of immunotherapy: sintilimab 3. surgery and 3 cycles of adjuvant chemotherapy using SOX regimen plus sintilimab. 4. S-1 administration till 1 year after surgery

Drug: SOX neoadjuvant; Drug: Sintilimab neoadjuvant; Procedure: gastrectomy plus D2 lymph node dissection; Drug: SOX adjuvant, Sequential S-1; Drug: Sintilimab adjuvant

Interventions

Oxaliplatin by arterial infusion plus S-1 DRUG

3 cycles oxaliplatin by arterial infusion plus S-1 every 21 days as neoadjuvant chemotherapy.

Arterial infusion group

SOX neoadjuvant DRUG

3 cycles of SOX neoadjuvant chemotherapy every 21 days.

SOX group

Sintilimab neoadjuvant DRUG

3 cycles of neoadjuvant immunotherapy every 21 days.

Arterial infusion group; SOX group

gastrectomy plus D2 lymph node dissection PROCEDURE

All patients, whose lesions are resectable and medically operable after 3 cycles neoadjuvant chemotherapy, will receive gastrectomy plus D2 lymph node dissection.

Arterial infusion group; SOX group

SOX adjuvant, Sequential S-1 DRUG

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.

Arterial infusion group; SOX group

Sintilimab adjuvant DRUG

3 cycles of adjuvant immunotherapy every 21 days.

Arterial infusion group; SOX group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

Gastrointestinal Department of Second Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

S 1 (combination); Gastrectomy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Shenbin XU, Doctor

CONTACT

86-15057315353; shenbin_xu@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Gastrointestinal Surgery, Second affiliated hospital of Zhejiang university School of Medicine

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: October 25, 2022
• Study Start: April 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)