A Phase 2 Trial of Optimizing Platinum-Based Chemotherapy Based on ERCC1 Expression as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ERCC1(excision repair cross-complementation 1 ) expression has effects on platinum-based chemotherapy for patients with locally advanced or metastatic gastric cancer, and to explore if ERCC1 can act as a biological predictor for the individual therapy of gastric cancer

Detailed Description
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This is a prospective, multi-center, randomized control clinical trial, aimed to demonstrate if ERCC1 expression could predict the efficacy of platinum-based chemotherapy in patients with locally advanced or metastatic gastric cancer. A total of 180 patients are planned to be enrolled into the study. ERCC1 protein expression in paraffin-embedding tumor tissue is examined by immunohistochemistry (IHC). Patients with low ERCC1 expression (group L) will be treated with XP regimen. Patients with high ERCC1 expression will be randomized into group H-A or group H-B, and be treated with XP or DX regimen, respectively. The primary end point is progression free survival (PFS), and the secondary end points include the median overall survival, objective response rate (ORR),disease control rate(DCR), duration of response, safety(number and degree of adverse events), and the quality of life (QOL).

Official Title
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A Prospective, Multi-Center, Randomized Control Phase 2 Trial of Optimizing Platinum-Based Chemotherapy Based on ERCC1 Expression as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: Capecitabine+Cisplatin
* Drug: Docetaxel+Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18y≤Age≤65y, male or female KPS≥70 Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease At least one measurable lesion, according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), assessed using imaging techniques (CT or MRI) No prior anti-tumor treatment or an interval of at least 6 months from the last adjuvant chemotherapy, and an interval of at least 4 weeks from the last radical radiation therapy No major organ disorder, with normal liver, kidney and heart function Laboratory test must meet the following criteria: hemoglobin (HGB) ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥100×109/L, creatinine clearance rate (CCr) ≥60ml/min, total bilirubin (TBil) ≤1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 UNL (For patients with liver metastasis, the AST/ALT must be ≤5.0 UNL), blood glucose ≤11.1 mmol/L Life expectancy of at least 12 weeks Signed informed consent For women with child bearing potential, a negative serum or urine pregnancy test result should be obtained before enrollment Exclusion Criteria: Progression from prior palliative treatment with capecitabine- or docetaxel-based regimen Serious uncontrolled systemic illness or medical condition: congestive heart failure, unstable angina, history of documented myocardial infarction within 6 months, uncontrolled hypertension and high risk uncontrollable arrhythmias; Obvious neurological or mental abnormalities including mental disorder, epileptic dementia, which affect compliance; Uncontrolled acute infections; Uncontrolled peptic ulcer, diabetes or other contraindication for corticosteroid therapy Inability to take or absorb oral medicine Concurrent administration of any other investigational drug, or have been enrolled in other clinical trial with investigational drug treatment within the 30 days of start of study treatment Presence of neuropathy ≥grade 1 according to NCI-CTCAE V4.0 Hypersensitivity or known or suspicious allergic to any of the study drugs Pregnant or lactated women Unsuitable for the study or other chemotherapy determined by investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: H-A: ERCC1 High Expression Group A<br>XP：Capecitabine+Cisplatin | Drug: Capecitabine+Cisplatin<br>* Cisplatin 75mg/m2, d1; Capecitabine 1700-2000mg/m2/day on days1-14 every 21 days, 6 cycles.Capecitabine is to be continued until disease progression or intolerable toxicity.<br>* Other names: Xeloda;|
| Experimental: H-B: ERCC1 High Expression Group B<br>DX：Docetaxel+Capecitabine | Drug: Docetaxel+Capecitabine<br>* Docetaxel 75mg/m2, d1; Capecitabine 1700-2000mg/m2/day on days1-14 every 21 days, 6 cycles. Capecitabine is to be continued until disease progression or intolerable toxicity.<br>* Other names: Xeloda;|
| Active Comparator: L: ERCC1 Low Expression Group<br>XP：Capecitabine+Cisplatin | Drug: Capecitabine+Cisplatin<br>* Cisplatin 75mg/m2, d1; Capecitabine 1700-2000mg/m2/day on days1-14 every 21 days, 6 cycles.Capecitabine is to be continued until disease progression or intolerable toxicity.<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival(OS) |  | 2 years | 
| Objective Response Rate(ORR),Including Complete Response(CR) and Partial Response(PR) |  | 2 years | 
| Disease Control Rate(DCR), Including Complete Response(CR) , Partial Response(PR) and Stable Disease(SD) |  | 2 years | 
| Duration of Response |  | 2 years | 
| Safety(number and degree of adverse events) |  | 2 years | 
| Quality of Life(QOL) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ERCC1, Gastric Cancer, Platinum, Chemotherapy