Trial of Adjuvant Chemotherapy for Gastric Cancer

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy of the intraperitoneal chemotherapy with early mitomycin administration and adding cisplatin to prolonged treatment with doxifluridine compared to mitomycin plus doxifluridine in resected advanced gastric cancer.

Detailed Description
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Stomach cancer is the most common cancer in Korea and one of the major health problems worldwide. The most effective treatment for gastric cancer is curative surgical resection of primary tumor. However, a substantial number of patients eventually die of recurrences after curative resection. A number of randomized trials investigating the role of adjuvant chemotherapy have been conducted. However, the efficacy of adjuvant chemotherapy is still controversial and varied between Western and Asian trials. Meta-analysis of Western trials didn't demonstrate the benefit of adjuvant chemotherapy after curative resection. Conversely, some Asian studies have demonstrated the efficacy of adjuvant chemotherapy after curative resection. In a previous study, mitomycin plus tegafur prolonged the survival in resected gastric cancer compared to no treatment. This study is designed to evaluate the efficacy of the intraperitoneal chemotherapy with early mitomycin administration and adding cisplatin to prolonged treatment with doxifluridine compared to mitomycin plus doxifluridine.

Official Title
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A Phase III Randomized Controlled Trial of Adjuvant Chemotherapy for Gastric Adenocarcinoma: Mitomycin and Doxifluridine Versus Intraperitoneal Chemotherapy and Mitomycin, Doxifluridine, and Cisplatin

Conditions
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Stomach Cancer

Intervention / Treatment
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* Drug: cisplatin, mitomycin-C, doxifluridine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven gastric adenocarcinoma Grossly serosa invasion of primary tumor is suspicious Curative resection was done Stage II, IIIA, IIIB, IV (including T4, lesions or N3, but excluding M1 lymph node metastasis) Age: 18-69 years old Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2 Adequate bone marrow function (white blood cell counts ≥ 4,000/ul, platelet count ≥ 100,000/ul, hemoglobin ≥ 10 g/dl) Adequate renal function (serum creatinine≤ 1.5) Adequate liver function (serum bilirubin ≤1.5 mg/dl, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x normal upper limit) Written informed consent was signed by the patient Exclusion Criteria: Previous chemotherapy or radiotherapy Active ongoing infection which antibiotic treatment is needed Pregnant or lactating women Psychosis or convulsion disorder Ascites in preoperative abdomen computed tomography (CT) Systemic disease which interfere the administration of chemotherapy Postoperative pathologic stage IA, IB Postoperative pathology indicates that resection margin is involved Previous history of other malignancy except cured non-malignant skin cancer and uterine cervical cancer in situ

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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: Mitomycin-C, Doxifluridine<br>Mf: Mitomycin-C 20mg/m2 intravenously (3-6 weeks after surgery) Doxifluridine 460-600mg/m2/day per oral for 3 months (started 4 weeks after surgery) | Drug: cisplatin, mitomycin-C, doxifluridine<br>* Mf: Mitomycin-C 20mg/m2 intravenously (3-6 weeks after surgery) Doxifluridine 460-600mg/m2/day per oral for 3 months (started 4 weeks after surgery) iceMFP: Cisplatin 100mg with 1L of normal saline intraperitoneally for 2 hours during surgery Mitomycin-C 15mg/m2 intravenously (1 day after surgery) Doxifluridine 460-600mg/m2/day per oral(started at 4 weeks after surgery and administered a total of 12 months) Cisplatin 60mg/m2 intravenously monthly for 6 months (started at 4 weeks after surgery)<br>|
| Active Comparator: Mitomycin-C, Doxifluridine, Cisplatin<br>iceMFP: Cisplatin 100mg with 1L of normal saline intraperitoneally for 2 hours during surgery Mitomycin-C 15mg/m2 intravenously (1 day after surgery) Doxifluridine 460-600mg/m2/day per oral(started at 4 weeks after surgery and administered a total of 12 months) Cisplatin 60mg/m2 intravenously monthly for 6 months (started at 4 weeks after surgery) | Drug: cisplatin, mitomycin-C, doxifluridine<br>* Mf: Mitomycin-C 20mg/m2 intravenously (3-6 weeks after surgery) Doxifluridine 460-600mg/m2/day per oral for 3 months (started 4 weeks after surgery) iceMFP: Cisplatin 100mg with 1L of normal saline intraperitoneally for 2 hours during surgery Mitomycin-C 15mg/m2 intravenously (1 day after surgery) Doxifluridine 460-600mg/m2/day per oral(started at 4 weeks after surgery and administered a total of 12 months) Cisplatin 60mg/m2 intravenously monthly for 6 months (started at 4 weeks after surgery)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free Survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity Profile (According to NCI CTC Version 2.0) | Because safety profile in oncology study is evaluated for each toxicity, it is impossible to present the overall patient number. Instead, we presented the number of patients who declined study therapy due to adverse events or patient will. | up to 1 year | 
| Overall Survival |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stomach cancer, adjuvant chemotherapy, mitomycin, cisplatin, doxifluridine