Perioperative Oxaliplatin With S-1 Combined H. Pylori Eradication in the Management of Locally Advanced Gastric Cancer

Phase 2

Not yet recruiting

• Conditions: Chemotherapy Effect
• Interventions: Drug: Oxaliplatin With S-1 (SOX) Combined H. Pylori Eradication (Amoxicillin + clarithromycin + omeprazole + colloidal bismuth subcitrate); Drug: Oxaliplatin With S-1 （SOX）

• Registration Number: NCT06510010
• Lead Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Brief Summary

This study focuses on patients with H. pylori-positive resectable locally advanced adenocarcinoma of the gastric and oesophagogastric junction. It evaluates the perioperative oxaliplatin with S-1 (SOX) combined H. pylori eradication versus oxaliplatin with S-1 in the management of H. pylori-positive locally advanced adenocarcinoma of the gastric and oesophagogastric junction (cT3/4a Nx or T2 N2/3, M0) , assessing their values and advantages.

Detailed Description

Subjects randomized to the trial group will receive 3-4 cycles of oxaliplatin with S-1 (SOX)+ H. pylori eradication (a 14-day quadruple regimen: amoxicillin + clarithromycin + omeprazole + bismuth potassium citrate) before surgery. One of the SOX regimens will be every 3 weeks (Q3W), with a tumor response assessment at the end of the neoadjuvant therapy course. Patients will continue to receive 4-5 cycles of SOX adjuvant chemotherapy after surgery for a total of 8 cycles of SOX regimen treatment. Patients in the trial group will undergo H. pylori eradication at the time of the first cycle of the SOX regimen. H. pylori eradication will be determined by postoperative pathology, and those who are H. pylori-positive by postoperative pathology will be treated with remedial eradication therapy after recovery from surgery (except for patients with total gastric resection).

Subjects randomized to the control group will receive 3-4 cycles of neoadjuvant therapy with the SOX regimen before surgery. The SOX regimen will be administered every 3 weeks (Q3W). A tumor response assessment will be performed at the end of the treatment course. Control patients were treated with H. pylori eradication after recovery from surgery based on postoperative pathologic H. pylori results: if H. pylori-positive, they received H. pylori eradication plus 4-5 cycles of SOX adjuvant chemotherapy (except for patients who underwent total gastric resection); if H. pylori-negative, they received 4-5 cycles of SOX adjuvant chemotherapy only.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-07-18
• Last Update Submitted: 2024-07-18
• Study First Posted: 2024-07-19
• Last Update Posted: 2024-07-19
• Study Start: 2024-07-31
• Primary Completion: 2026-02-28
• Study Completion: 2028-07-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 198

Inclusion Criteria

1. have been fully informed about the study and voluntarily signed the informed consent form (ICF);

2. Gastroscopy pathology confirmed locally advanced adenocarcinoma of the gastric and oesophagogastric junction (Siewert type I-III);

3. Clinical (enhanced CT, enhanced MRI, or PET-CT) staging at the time of diagnosis: cT3/4a Nx or T2 N2/3, M0 (The American Joint Committee on Cancer 8th edition):

4. The present H. Pylori infection at the time of diagnosis is determined by one of the following 3 items: ① Positive gastric mucosal tissue rapid urease test (RUT), tissue section staining, or bacterial culture for any of the 3 items. Positive 13C or 14C-urea breath test (UBT). ③ Positive helicobacter pylori stool antigen (HpSA) tests (clinically validated monoclonal antibody method). Positive serum H. Pylori antibody test (clinically proven reagent with high accuracy) suggests previous infection, and those who have never been treated can be considered as having current infection;

5. Sex is not limited and age is 18-75 years old;

6. Eastern Cooperative Oncology Group (ECOG) score 0-1;

7. Organ function permits major abdominal surgery;

8. Expected survival ≥ 6 months;

9. Laboratory test values must meet the following criteria within 7 days prior to enrollment:

   1. whole-body cryotherapy/cryostimulation (WBC) > 4.0 × 10^9/L and < 15 × 10^9/L, ANC > 1.5 × 10^9/L, Hb ≥ 75 g/L, PLT ≥ 100 × 10^9/L;
   2. Serum bilirubin ≤ 1.5 x high limit of normal, aspartate transaminase (AST), alanine aminotransferase (ALT) ≤ 2.5 x high limit of normal;
   3. Creatinine ≤ 1.5 x high limit of normal or creatinine clearance rate > 60 ml/min;
   4. international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × Upper limit of normal ( ULN ) only for subjects not receiving anticoagulation; subjects receiving anticoagulation should be on a stable dose;

10. Ability to cooperate with the appropriate endoscopic, laboratory and imaging tests for this protocol;

11. Females of childbearing potential (including females who are menopausal due to chemo-menopause or other medical reasons) must agree to use contraception for a period of at least 6 months from the time of signing the Informed Consent Form to at least 6 months after the last dose of study treatment or concomitant chemotherapy, whichever is later. Females must also agree to refrain from breastfeeding for a period of at least 6 months from the time of signing the informed consent to the time of the last administration of the study drug or concomitant chemotherapy, whichever is later; males must agree to use contraception for a period of at least 6 months from the time of administration of the test drug to the time of the last administration of the test drug or concomitant chemotherapy, whichever is later.

Exclusion Criteria

1. Stage IV or unresectable gastric or gastroesophageal junction cancer as determined by the investigator;
2. Other active malignancies within 5 years or concurrently.
3. Patients who are preparing for or have previously received organ or bone marrow transplantation;
4. Myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥ 450 ms in men and ≥ 470 ms in women) within 6 months prior to the first dose (QTc interval is calculated by the Fridericia formula);
5. Presence of New York Heart Association (NYHA) class III-IV cardiac insufficiency or cardiac ultrasound: LVEF (left ventricular ejection fraction) < 50%;
6. Presence of active pulmonary tuberculosis by history or CT, or patients with a history of active pulmonary tuberculosis within 1 year prior to enrollment, or patients with a history of active pulmonary tuberculosis more than 1 year prior but without regular treatment;
7. Presence of a known active or suspected autoimmune disease. The exception is those who are in a stable state of that disease at the time of enrollment (not requiring systemic immunosuppression therapy);
8. Received a live vaccine within 28 days prior to the first dose; except inactivated viral vaccines for seasonal influenza;
9. Patients requiring treatment with systemic corticosteroids (> 10 mg/day prednisone efficacy dose) or other immunosuppressive drugs within 14 days prior to first dose or during the study period. However, enrollment is permitted if patients are allowed to be treated with topical topical or inhaled steroids, or adrenal hormone replacement therapy at doses ≤ 10 mg/day prednisone efficacy dose in the absence of active autoimmune disease;
10. Undergoing treatment in another clinical study or scheduled to begin treatment in this study less than 14 days from the end of treatment in the previous clinical study;
11. Known history of severe allergy to any study drug excipients;
12. known history of psychotropic pharmaceuticals abuse or drug addiction; patients who have stopped drinking alcohol can be enrolled;
13. Presence of patients with conditions that may increase the risk of study medication, or other severe, acute and chronic medical conditions that, in the judgment of the investigator, make participation in a clinical study unsuitable.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oxaliplatin With S-1 （SOX）Combined H. Pylori Eradication	Oxaliplatin With S-1 (SOX) Combined H. Pylori Eradication (Amoxicillin + clarithromycin + omeprazole + colloidal bismuth subcitrate)	Subjects randomized to the trial group will receive 3-4 cycles of Oxaliplatin With S-1 （SOX）+ H. pylori eradication (a 14-day quadruple regimen: amoxicillin + clarithromycin + omeprazole + bismuth potassium citrate) before surgery. One of the SOX regimens will be every 3 weeks (Q3W), with a tumor response assessment at the end of the neoadjuvant therapy course. Patients will continue to receive 4-5 cycles of SOX adjuvant chemotherapy after surgery for a total of 8 cycles of SOX regimen treatment. Patients in the trial group will undergo H. pylori eradication at the time of the first cycle of the SOX regimen. H. pylori eradication will be determined by postoperative pathology, and those who are H. pylori-positive by postoperative pathology will be treated with remedial eradication therapy after recovery from surgery (except for patients with total gastric resection).
Oxaliplatin With S-1 （SOX）	Oxaliplatin With S-1 （SOX）	Subjects randomized to the control group will receive 3-4 cycles of neoadjuvant therapy with the Oxaliplatin With S-1（SOX）regimen before surgery. The SOX regimen will be administered every 3 weeks (Q3W). A tumor response assessment will be performed at the end of the treatment course. Control patients were treated with H. Pylori eradication after recovery from surgery based on postoperative pathologic H. Pylori results: if H. Pylori-positive, they received H. Pylori eradication plus 4-5 cycles of SOX adjuvant chemotherapy (except for patients who underwent total gastric resection); if H. Pylori-negative, they received 4-5 cycles of SOX adjuvant chemotherapy only.

Primary Outcome Measures

Name	Time	Method
major pathological response (MPR)	Through postoperative pathology, an average of 2 week	MPR defined as a tumor regression grade (TRG) score of 0-1; TRG 0 represents complete remission (no residual cancer cells), TRG 1 meant significant remission (residual lesions \< 10%)

Secondary Outcome Measures

Name	Time	Method
pathological complete response (pCR)	Through postoperative pathology, an average of 2 week	pCR defined as tumor regression grade (TRG) score of 0；TRG 0 represents complete remission (no residual cancer cells)
serious adverse events (SAE)	From the beginning of the first neoadjuvant chemotherapy to 60 days after the last adjuvant chemotherapy	Serious adverse events (SAE) means an adverse medical event resulting in death, life-threatening, permanent or severe disability or loss of function, the need for or prolongation of hospitalization of the subject, and congenital anomalies or birth defects after the subject has received the experimental medication.
overall survival （OS）	From date of first administration until the date of death from any cause, assessed up to 36 months"	Overall survival （OS） refers to the time from the beginning of randomization to death from any cause.
adverse events (AE)	From the beginning of the first neoadjuvant chemotherapy to 60 days after the last adjuvant chemotherapy	Adverse events (AE) means all adverse medical events that occur after the subject has received the experimental medication.
disease-free survival (DFS)	From the date of first administration until the date of first disease recurrence or date of death from any cause, whichever came first, assessed up to 36 months.	Disease-free survival (DFS) refers to the time from the beginning of randomization to the recurrence of the disease or death from any cause (whichever occurs first).
R0 resection rate	Through postoperative pathology, an average of 2 week	No cancer cells could be found at the cut edge of the specimen under the microscope, and no cancer cells remained either visually or microscopically; the lesion was completely removed.