Study of Perioperative Chemotherapy Combined With Tirelizumab and Trastuzumab in the Treatment of GC/EGC

• Status: Not yet recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of tirelizumab and trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and the investigators aimed to explore its role in the perioperative setting.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University
• Treatments: Docetaxel; Oxaliplatin; Trastuzumab

Criteria

Key Inclusion Criteria:

• provide archive tumor tissue samples or accept fresh tumor tissue biopsy(Sample requirements are: formalin-fixed and paraffin-embedded wax blocks of tumor tissue or at least 20 unstained tumor specimen slides).

• assessed by the surgery can be removed, histology/confirmed HER2 positive cytology and the integration of a stomach esophagus carcinoma.

• CT2-4CN any C M0 or T any CN +M0, AJCC/UICC TNM staging of gastric cancer (8th edition).

• The HER2 receptor protein status was assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) using the following methods.Tumors with an IHC 3+ score are considered HER2-positive.Patients with immunohistochemical 2+ tumors were given FISH tests to determine FISH positive samples.

• Abdominal computed tomography (CT), abdominal, pelvic, and/or echo-endoscopy were performed 2 weeks before surgery to assess resectability.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2.

• have no received no any anti-tumor treatment, including surgery, chemotherapy, targeted therapy, immune therapy.

• Adequate organ function (No blood transfusion or hematopoietic stimulating factor therapy was received within 14 days. Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥75×109/L Hemoglobin ≥80 g/L. Serum total bilirubin ≤1.5×ULN. total bilirubin must be <3×ULN) Prothrombin time/international normalized ratio (PT/INR) ≤1.5×ULN and activated partial thromboplastin time (aPTT) ≤1.5×ULN.Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3×ULN. For subjects with liver metastases, AST and ALT must be ≤5×ULN for subjects with liver metastases. Creatinine clearance rate (Ccr) ≥50ml/min（according to the Cockcroft-Gault formula）. Urine protein qualitative≤1+ ;Or urinary protein qualitative ≥2+, 24 hours urinary protein < 1g)

Key Exclusion Criteria:

• A history of any other malignancy in the past 5 years (except carcinoma in situ or basal cell carcinoma of the skin or squamous cell carcinoma of the skin)

• Received other unmarketed investigational drug or therapy within 4 weeks prior to initial investigational drug use.

• A major organ surgery (excluding needle biopsy) or significant trauma occurred within 4 weeks prior to initial investigational drug use.

• Requires systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration to treat a current condition.

Exceptions include: topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids;Short-term use of glucocorticoids for preventive treatment (e.g. to prevent contrast allergy)

• Use of immunoregulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., within 14 days prior to initial use of the study drug.

• Has been administered a live vaccine within 4 weeks prior to Cycle1 Day 1.

• Previous recipient of allogeneic hematopoietic stem cell transplantation or organ transplantation.

• Previous adverse reactions to other medications have not recovered to CTCAE 5.0 level ≤1 (Other toxicities, such as hair loss, were not considered to pose a safety risk).

• Symptomatic peripheral neuropathy was evaluated as > 2 with CTCAE 5.0.

• Has central nervous system metastases or meningeal metastases.

• Inability to swallow medications orally, or other gastrointestinal diseases (such as total intestinal obstruction, etc.) that may affect the absorption of oral medications.

• Patients who had an active infection within 1 week prior to the first use of the study drug and who currently require systemic anti-infective therapy.

• has a history of alcohol or drug abuse or dependence.

• Known history of Human Immunodeficiency Virus (HIV).

• Untreated chronic hepatitis B viral (HBV) infection or chronic HBV carrier with HBV DNA ≥200 IU/mL (or 1000 copies/mL),prophylaxis antiviral therapy other than interferon is allowed ,or active hepatitis C virus (HCV) should be excluded.

• Current patients with interstitial lung disease.

• Has a history of severe cardiovascular and cerebrovascular disease, including but not limited to: has serious heart rhythm or abnormal conduction;Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to D1 ;New York heart association (NYHA), cardiac function class II or higher and left ventricular ejection fraction (LVEF) < 50%; clinical uncontrol of high blood pressure.

• Patients with active, or previous and recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) were excluded from patients with clinically stable autoimmune thyroid disease.

• Grade 3 or higher arteriovenous thromboembolism events or bleeding events occurred within 6 months prior to the first use of the study drug;Or present with grade ≥2 bleeding or factors determined by the investigator to have a higher blood risk (such as active gastrointestinal ulcer or esophageal varicose veins or tumor invasion of major blood vessels).

• Gastrointestinal perforation, abdominal fistula or intraperitoneal abscess occurred within 6 months prior to the first use of the study drug;Or a risk factor for cavity perforation/fistula formation (e.g., tumor infiltration of the outer wall of the cavity wall) currently identified by the investigator.

• Patients who allergies to the study drugs.

• People with mental disorders or poor compliance.

• Women who are pregnant or lactating.

• The investigator considers the subject to have a history of other serious systemic disease or for other reasons unsuitable for participation in this clinical study.