Genotype-drive Study of Irinotecan-Cisplatin Combination for Advanced Gastric Cancer

Genotype-drive Phase II Study of Novel Irinotecan-Cisplatin Combination as First-line Therapy for Advanced Gastric Cancer

The purpose of this study is to evaluate the efficacy and safety of first-line chemotherapy with cisplatin and irinotecan in advanced gastric cancer, and try to find out the optimal dosage of combination chemotherapy.

Open label single arm phase II study of cisplatin and irinotecan in patients with advanced gastric carcinoma not previously treated with palliative chemotherapy. 40 Patients will be enrolled in this local trial. The primary objective of this study is to determine the response rate of the treatment.Schedule for this study is as follows: 8 cycles/14 days of irinotecan 125 mg/m2 on Day 1 and cisplatin 50 mg/m2 on Day2. This study will also include genotype investigations of UGT1A1 and ERCC1 expression in order to assess determinants of efficacy and toxicity of the treatment with cisplatin and irinotecan in the study population.

Inclusion Criteria:

• Histologically proven diagnosis of adenocarcinoma of the stomach (including adenocarcinoma of the gastroesophageal junction)
• Stage III or Stage IV disease, according to American Joint Committee on Cancer criteria
• Patients with UGT1A1*28 genotype 6/6 or 6/7
• Performance Status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance status Scale
• Previous adjuvant or pre-operative chemotherapy without containing irinotecan or platinum at least 6 months before enrollment
• Adequate organ function including the following:

Bone marrow: absolute neutrophil count (ANC) >or equal to 1.5 * 109/L, platelets >or equal to 100 *109/L, hemoglobin > or equal to 10 g/dL.

Hepatic: bilirubin < or equal to 1.5 x ULN; alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) < or equal to 3 x ULN (alkaline phosphatase, AST, ALT minor or equal to 5 x ULN is acceptable if liver has tumor involvement), serum albumin > or equal to3g/dL.

Renal: Calculated creatinine clearance major or equal to 60 ml/min (using the standard Cockcroft-Gault formula).

Exclusion Criteria:

• No Prior palliative chemotherapy for advanced disease
• Previous radiation therapy is allowed but should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed at least 30 days before study enrollment
• Known or suspected brain metastasis
• Second primary malignancy