Phase 3 Study of Xelox Followed by Maintenance Capecitabine in the Advanced Gastric Cancer

Study Overview
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Brief Summary
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XELOX regimen had a more favorable toxicity profile compared to cisplatin for patients with advanced gastric cancer. The safety profile of oxaliplatin makes it an ideal candidate for combination therapy. However, oxaliplatin induce sensory neuropathy, a cumulative, dose-related toxicity. It may therefore be possible to devise capecitabine maintenance regimen which achieves maximum treatment effect before cumulative neurotoxicity appears. We study that randomized Phase III study of Xelox (Capecitabine plus Oxaliplatin) followed by maintenance Capecitabine or Observation in the gastric cancer patients of stable disease after 6 cycle 1st line of XELOX chemotherapy .

Detailed Description
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Study rationale : Park et al. observed the oxaliplatin as part of XELOX regimen had a more favorable toxicity profile compared to cisplatin for patients with advanced gastric cancer. The safety profile of oxaliplatin makes it an ideal candidate for combination therapy. However, oxaliplatin induce sensory neuropathy, a cumulative, dose-related toxicity. The response with XELOX regimen generally occurs earlier. It may therefore be possible to devise capecitabine maintenance regimen which achieves maximum treatment effect before cumulative neurotoxicity appears. This regimen was studied in colon and breast cancer. - Objective: Primary: To evaluate progression free survival Secondary: To evaluated overall survival, response rate, toxicity profile of chemotherapy, quality of life Design :Multicenter randomized controlled phase III open label trial Study subjects will be randomized to two groups in a ratio of 1:1 Subjects More than stable disease after 6 cycle 1st line of XELOX chemotherapy (OR non-complete response/non-progressive disease in cases of non-measurable disease before XELOX chemotherapy), Treatment Groups Group A : Capecitabine: Capecitabine 1000mg/m2 bid D1-14, q 3 week Group B : Observation Evaluation of response and toxicity A response will be evaluated radiologically every two cycles thereafter, or when progression is suspicious by RECIST criteria version 1.1. A progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause. An overall survival is defined as the time from the 1stdate of chemotherapy to the date of death. Safety will be evaluated every treatment by NCI-CTCAE version 4.0.

Official Title
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Randomized Phase 3 Study of Xelox(Capecitabine Plus Oxaliplatin) Followed by Maintenance Capecitabine or Observation in Patients With Advanced Gastric Adenocarcinoma

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven gastric cancer Minimum age of 18 years Stage IV (regardless of the presence or absence of measurable disease by RECIST criteria) or recurrent after curative surgery Negative expression (0, 1) of Her2 Immuno-histochemistry or negative amplification of FISH in Her2 Immuno-histochemistry 2+ More than stable disease after 6 cycle 1st line of XELOX chemotherapy (OR non-Complete response/non-Progressive disease in cases of non-measurable disease before XELOX chemotherapy) Eastern Cooperative Oncology Group Performance status 0-2 Adequate bone marrow function: Absolute neutrophil count ≥ 1,500/ul, Hemoglobin ≥ 8 g/dL, platelet ≥ 100,000/μl Adequate renal function: Serum creatinine ≤ 1.5 x ULN (upper normal limit) or creatinine clearance ≥ 60 ml/min Adequate hepatic function: serum bilirubin ≤ 2.5 x UNL, AST and ALT ≤ 2.5 x UNL (≤ 5 x ULN in the presence of liver metastasis) Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital Exclusion Criteria: Patients who were exposed previously to any chemotherapy except XELOX for advanced disease Patients who received R0 or R1 resection for metastatic or recurrent gastric cancer and without evaluable/measurable disease Disease relapsed during or within 4 months after adjuvant therapy Patients who had central nervous system and meningeal metastases Patients with significant neurologic or psychiatric disorders Patients with active infection, severe heart disease, uncontrollable hypertension or diabetes mellitus, myocardial infarction during the preceding 6 months, pregnancy, or breast feeding Any previous or concurrent malignancy except for adequately treated non-melanoma skin cancer, in situ cancer of uterine cervix, non-muscle invasive bladder cancer or malignancy without evidence of recurrence within 5 years

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| No Intervention: Group A<br>observational arm | |
| Experimental: Group B<br>arm of capecitabine maintenance treatment | Drug: Capecitabine<br>* maintenance capecitabine therapy after six cycles of XELOX<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 | every two cycles (6 weeks) until 18 weeks and then every 4 cycles (12 weeks) until progression | From date of randomization until the date of first documented progression, whichever came first, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | every two cycles (6 weeks) until 18 weeks and then every 4 cycles (12 weeks) until death | From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 years | 
| quality of life in patients measured by QLQ-c30 and STO-22 | every two cycles (6 weeks) until 18 weeks and then every 4 cycles (12 weeks) until progression | From date of randomization until the date of first documented progression, whichever came first, assessed up to 2 years | 
| Toxicity profile of each patients measured by NCI-CTCAE ver 4.0 | every two cycles (6 weeks) until 18 weeks and then every 4 cycles (12 weeks) until progression | From date of randomization until the date of first documented progression, whichever came first, assessed up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy, stomach neoplasms