Observational Study of Perioperative Chemotherapy in Gastric Cancer

Study Overview
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Brief Summary
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This study will assess the efficacy and toxicity of perioperative chemotherapy with Epirubicin + Cisplatin + Capecitabine (ECX) in routine clinical practice in a network of public hospitals in Santiago, Chile.

Detailed Description
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Chile belongs to the countries with a high mortality rate due to gastric cancer, and this disease is the most frequent cause of cancer death in Chile. Despite of adequate surgery, survival rates are disappointing, with less than 60% of patients for all stages achieving to be alive at 5 years. This is due to the fact that frequently gastric cancer is diagnosed at an advanced stage. For locally advanced gastric cancer a multimodality treatment is recommended, with the alternatives of surgery followed by chemotherapy (asian approach), surgery followed by chemoradiation (US approach) and perioperative chemotherapy (european approach). These three strategies are valid standard treatment options and have shown to improve overall survival in stage IB to IVA gastric cancer. Perioperative chemotherapy administered pre- and postoperatively, has shown to downstage the tumor, increase curative resection, progression free and overall survival. For patients with potentially resectable gastric cancer staged T2 or higher or cN+, NCCN Guidelines recommend perioperative chemotherapy (category1). Chilean guidelines for gastric cancer state the alternative of perioperative chemotherapy, however this approach has not been used widely in public hospitals because lack of financial support. Some gastric cancers overexpress HER2, and this subset of patients benefit from targeted therapy at an advanced stage. The proportions of patients with these molecular characteristics vary widely depending of the geographic area. The chilean population has been investigated in small series, but the incidence of HER2 positive gastric cancer is not known. We therefore plan to measure HER2 expression in all participating patients.

Official Title
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Prospective Observational Study of Patients With Locally Advanced Gastric Cancer Treated With Perioperative Chemotherapy and Surgery

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: epirubicin + cisplatin + capecitabine polychemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven invasive carcinoma Age > 18 years. ECOG performance status 0 or 1. Hemoglobin > 9 g/dL Absolute neutrophil count > 1.5 x 109/L Platelet count > 100 x 109/L Creatinine < 1.5 ULN Creatinine clearance > 60 mL/min Serum bilirubin < 1.5 x ULN AST < 2.5 x ULN Women of child bearing potential: must agree to use an effective contraceptive method. Signed informed consent. Exclusion Criteria: ECOG > 2. Pre-existing diarrhea uncontrolled with supportive care. Inability to swallow Xeloda tablets. History of mild-to-moderate renal insufficiency (creatinine clearance < 45 mL/min). Signs or symptoms of clinically significant hepatic dysfunction (bilirubin > 1.5 ULN, FA > 2.5 ULN, albumin < 2,5 g/dL). Significant cardiac dysfunction (LVEF < LLN) Presence of distant metastasis, including clinical signs of peritoneal carcinomatosis Symptomatic gastric retention or severe dysphagia with a caloric intake of < 1500 kcal/day Histology of lymphoma, GIST or neuroendocrine tumor Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use an effective method of contraception. Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include congestive heart failure of Class III or IV of the NYHA classification, infection requiring parental or oral treatment, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent.

Ages Eligible for Study
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Minimum Age: 19 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| locally advanced gastric cancer<br>Patients with resectable, locally advanced cT3-4 and/or N+ gastric carcinoma treated with 3 perioperative epirubicin cisplatin capecitabine polychemotherapy | Drug: epirubicin + cisplatin + capecitabine polychemotherapy<br>* EPIRUBICIN (LKM)at a dose of 50 mg/m2 over 15 minutes is administered every 21 days. CISPLATIN (LKM) at a dose of 60 mg/m2 over 4 hours is administered every 21 days. Patients must receive standardized hydration per protocol. CAPECITABINE (Xeloda®) at a dose of 625 mg/m2 BID (i.e. 1250 mg/m2/day) 30 minutes after meals from day 1 to day 21 of every cycle of chemotherapy. Antiemetic therapy: Dexamethasone 8 mg IV and Ondansetron (LKM) 8 mg IV o Granisetron (Kytril®) prior to chemotherapy Rescue Ondansetron (LKM) 8 mg IV will be given during 24-hour hospitalization in case of emesis Symptomatic antiemetic therapy with thiethylperazine will be prescribed. Loperamide will be prescribed in case of diarrhea.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of downstaging | To determine the rate of downstaging of locally advanced cT3-4 and/or N+ gastric carcinomas after 3 cycles of preoperative chemotherapy with ECX | through study completion, an average of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of adverse events | Rate and description of adverse events | through study completion, an average of 6 months | 
| Clinical response after three cycles of preoperative ECX | Clinical response based on RECIST criteria | through study completion, an average of 6 months | 
| To evaluate the surgical morbidity after three cycles of preoperative CT | Hospital stay duration | through study completion, an average of 1 year | 
| To evaluate the surgical mortality after three cycles of preoperative CT | 30 days postoperative mortality rate | through study completion, an average of 1 year | 
| progression free survival | To evaluate the 3 year progression free survival | through study completion, an average of 2 years | 
| overall survival | To evaluate the 5 year overall survival (OS) of patients treated with perioperative CT | through study completion, an average of 3 years | 
| compliance with the planned postoperative therapy | To evaluate the rate of start and completion of postoperative treatment | through study completion, an average of 1 year | 
| EORTC QLQ-C30 after neoadjuvant chemotherapy and surgery | To evaluate quality of life through patient reported outcomes of patients treated with perioperative chemotherapy | through study completion, an average of 2 years | 
| EORTC QLQ-STO 22 after neoadjuvant chemotherapy and surgery | To evaluate patient reported specific symptoms of patients treated with perioperative chemotherapy | through study completion, an average of 2 years | 
| HER 2 expression | To determine the number of patients with HER2 overexpressing gastric cancers | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, combination chemotherapy, HER-2 gene, quality of life