Nivolumab, S-1 Combined With Oxaliplatin Versus Nivolumab as Neoadjuvant Therapy in Advanced Gastric Cancer

NCT ID: NCT04782791

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2024-05-31

Brief Summary

The trial is a prospective, randomized, controlled phase Ⅱ study which will be conducted in Chinese PLA General Hospital, Beijing, China. Patients with eligibility will enrolled and assigned into either group A for 9 weeks of nivolumab, S-1 combined with oxaliplatin (Nivo+SOX) followed by D2 surgery and group B for 9 weeks of nivolumab followed by D2 surgery. The primary endpoint is the safety assessed by recording adverse events and the secondary endpoints are response rate, disease control rate, pathological complete response rate, D2 rate and R0 rate.

Conditions

Gastric Cancer; Chemotherapy Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nivo + SOX

Nivolumab plus SOX

Group Type: EXPERIMENTAL

Nivolumab plus SOX

Intervention Type: DRUG

The preoperative therapy consists of three-week cycles of intravenously administered nivolumab 360mg and oxaliplatin 130mg/m2 on day 1, and orally administered S-1 40-60 mg twice a day (BID) on day 1 to 14. The dose of S-1 depends on body surface area (BSA): BSA\<1.25 m2, 40mg; 1.25\<BSA\<1.50 m2, 50mg; BSA\>1.50 m2, 60mg. Day 15 to day 21 is the rest period.

Gastrectomy

Intervention Type: PROCEDURE

A standard D2 radical laparoscopic gastrectomy according to the CSCO clinical guidelines for the diagnosis and treatment of gastric cancer is planned 3-4 weeks after the last cycle of preoperative therapy.

Nivo

Nivolumab

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

The preoperative therapy consists of three-week cycles of intravenously administered nivolumab 360mg on day 1.

Gastrectomy

Intervention Type: PROCEDURE

A standard D2 radical laparoscopic gastrectomy according to the CSCO clinical guidelines for the diagnosis and treatment of gastric cancer is planned 3-4 weeks after the last cycle of preoperative therapy.

Interventions

Nivolumab plus SOX

The preoperative therapy consists of three-week cycles of intravenously administered nivolumab 360mg and oxaliplatin 130mg/m2 on day 1, and orally administered S-1 40-60 mg twice a day (BID) on day 1 to 14. The dose of S-1 depends on body surface area (BSA): BSA\<1.25 m2, 40mg; 1.25\<BSA\<1.50 m2, 50mg; BSA\>1.50 m2, 60mg. Day 15 to day 21 is the rest period.

Intervention Type: DRUG

Nivolumab

The preoperative therapy consists of three-week cycles of intravenously administered nivolumab 360mg on day 1.

Intervention Type: DRUG

Gastrectomy

A standard D2 radical laparoscopic gastrectomy according to the CSCO clinical guidelines for the diagnosis and treatment of gastric cancer is planned 3-4 weeks after the last cycle of preoperative therapy.

Intervention Type: PROCEDURE

Other Intervention Names

Nivo + SOX; Nivo

Eligibility Criteria

Inclusion Criteria

• Non-bedridden, aged 18 to 70 years old;
• Eastern Cooperative Oncology Group (ECOG) score is 0 to 1;
• Histologically confirmed gastric adenocarcinoma;
• Have evaluable lesions based on RECIST 1.1;
• Stage III (cT3-4aN1-3 M0, American Joint Committee on Cancer (AJCC) TNM staging system 8th edition) gastric cancer confirmed by enhanced computer tomography (enhanced CT) and laparoscopic exploration (endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) if necessary);
• The surgeon have the ability to complete standard D2 radical gastrectomy and the gastrectomy can be tolerated by the patient;
• Laboratory test criteria: peripheral blood hemoglobin (Hb) ≥ 90 g/L, neutrophil absolute count ≥ 3× 109 /L, platelet count (PLT) ≥ 100× 109 /L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), total bilirubin ≤ 1.5×ULN, serum creatinine (SCr) ≤ 1.5×ULN, and serum albumin (ALB) ≥ 30 g/L;
• Patients with heart disease, echocardiogram showing that the left ventricular ejection fraction ≥ 50%, electrocardiogram (ECG) is basically normal within 4 weeks before operation and with no obvious symptoms are acceptable;
• There is no serious underlying disease that could lead to an expected life expectancy < 5 years;
• Willing to sign the informed consent for participation and publication of results.

Exclusion Criteria

• Human epidermal growth factor receptor 2 (HER2)-positive or indeterminate G/GEJ cancer;
• Pregnant or lactating women;
• Positive pregnancy test for women in childbearing age. Menopausal women without menstruation for at least 12 months can be regarded as women with no possibility of getting pregnant;
• Refusal of birth control during the study;
• Prior chemotherapy, radiotherapy or immunotherapy;
• History of other malignant diseases in the last 5 years (except for cervical carcinoma in situ);
• History of uncontrolled central nervous system diseases, which could influence the compliance;
• History of severe liver diseases (Child-Pugh class C), renal diseases (endogenous creatinine clearance rate (Ccr) ≤ 50 ml/min or SCr > 1.5 ULN) or respiratory diseases; Uncontrolled diabetes and hypertension; Clinically severe heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure, uncontrolled arrhythmia requiring drug intervention, or a history of myocardial infarction in the last 6 months;
• History of dysphagia, complete or partial gastrointestinal obstruction, active gastrointestinal bleeding and gastrointestinal perforation;
• On steroid treatment after organ transplant;
• With uncontrolled severe infections;
• Known dihydropyrimidine dehydrogenase deficiency (DPD);
• Anaphylaxis to any research drug ingredient;
• Known peripheral neuropathy (> NCI-CTC AE 1). Patients with only disappearance of deep tendon reflex need not to be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lin Chen

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Xinxin Wang, Dr.

Role: CONTACT

301wxx@sina.com

+8613811858199

Other Identifiers

R3

Identifier Type: -

Identifier Source: org_study_id