T- XELOX in HER2-positive Stage III Gastric Cancer After D2 Gastrectomy

Study Overview
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Brief Summary
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The objective of this study is to assess the clinical efficacy and safety of trastuzumab plus XELOX for treatment of HER2-positive Stage III Gastric Cancer After D2 Gastrectomy.

Detailed Description
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Gastric cancer is the second leading cause of cancer death worldwide. Highest incidence rate is observed in Eastern Asia. D2 gastrectomy has been established as a standard surgical procedure. While recurrence rate after resection is still high. The CLASSIC study showed that Xelox regimen after D2 gastrectomy improves 3-year disease-free survival compared with surgery only. But patients with late stage still have poor prognosis according to subgroup analysis and our retrospective study. HER2 is an important biomarker and key driver of tumorigenesis in 7-34% gastric cancers. The ToGA study showed that trastuzumab, a monoclonal antibody that targets HER2, plus chemotherapy improved overall survival(16.0m vs 11.8m) in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. Based on previous experiences of trastuzumab in adjunctive therapy of breast cancer and ACTS/CLASSIC/ToGA studies, we suppose that trastuzumab plus XELOX as adjunctive treatment may benefit patients with HER2-positive Stage III gastric cancer after D2 Gastrectomy. According to the above, we do this single-arm research to assess the clinical efficacy and safety of trastuzumab plus XELOX for treatment of HER2-positive Stage III Gastric Cancer After D2 Gastrectomy.

Official Title
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Trastuzumab Plus XELOX for HER2-positive Stage III Gastric Cancer After D2 Gastrectomy：Prospective Observational Study.

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Trastuzumab
* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed-consent form. Aged 18-80 years. Had partial or total D2 gastrectomy and achieved R0 resection. Histologically confirmed gastric or gastro-oesophageal junction adenocarcinoma，mucinous adenocarcinoma ，signet-ring cell carcinoma Pathologic Stage III (IIIA-C). HER2-positive: (IHC 3+ or IHC 2+ and FISH positive). Patients must have received no preoperative chemotherapy or radiation therapy. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 . Adequate liver/bone marrow function.Blood and biochemical parameters; Compliant, and can be followed up regularly. Exclusion Criteria: Patients who do not meet the Inclusion Criteria. Pregnant or breast-feeding female, or not willing to take contraception measures during study. Serious infection requiring antibiotics intervention during recruitment. Allergic to study drug or with metabolism disorder. Histologically confirmed small cell carcinoma of the stomach、gastric neuroendocrine carcinoma or others. Uncontrolled brain metastasis or mental illness. Organ transplant recipients (Autologous transplantation of bone marrow and peripheral stem cell transplantation included). Congestive heart failure, uncontrolled cardiac arrhythmia, etc. With severe hepatic/kidney/respirator/disease,or chronic disease like uncontrolled diabetes,hypertension,etc. with other malignant tumors. Can be followed up or obey protocol. Ineligible by the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab,Capecitabine,Oxaliplatin<br>Patients receive eight 3-week cycles of oral capecitabine (800-1000 mg/m2 twice daily on days 1-14 of each cycle) ,intravenous oxaliplatin (130 mg/m2 on day 1 of each cycle) plus intravenous Trastuzumab (440mg on day 0 of each cycle). Number of cycle:capecitabine and oxaliplatin --8 cycles; Trastuzumab--14-16 cycles. | Drug: Trastuzumab<br>* Trastuzumab is given by intravenous infusion at 440mg on day 0every 3 weeks. Number of cycles: 14 16 cycles.<br>* Other names: Herclon;Drug: Capecitabine<br>* Capecitabine 800 1000 mg/m² is given orally twice a day for 14 days followed by a 1-week rest. Number of cycles: 8 cycles.<br>* Other names: Xeloda;Drug: Oxaliplatin<br>* Oxaliplatin is given by intravenous infusion at 130 mg/m2 on day 1 every 3 weeks. Number of cycles: 8 cycles.<br>* Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival (DFS) | Defined as the time from study treatment to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. | Measure at every 6 weeks (every 2 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Measure of time from study treatment to patient's death or lost to follow-up. | up to 3 years | 
| Safety and tolerability | Percentage of patients who experience adverse events during this study. | up to 18 month | 
| Prognostic value of biomarkers | assessment of the relationship between biomarker status and prognosis | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, HER2-positive, Trastuzumab, Stage III, D2 Gastrectomy, XELOX