Irinotecan Versus Only Best Supportive Care for Gastric Cancer

Randomized Phase III Study With Irinotecan+Best Supportive Care Versus Only Best Supportive Care as Second Line Therapy for Metastatic Gastric Cancer

The median survival at progression after first-line chemotherapy for metastatic gastric cancer is about 2.5 months. There are no data which a possible benefit of second line therapy. for this reason a trial which investigates a possible benefit or chemotherapy compared to best supportive care as second line treatment is urgently necessary.

Irinotecan shows response rates of 20% in the first line therapy with high rates od disease stabilization. There are few trials investigating irinotecan in the second line setting. Response rates of 20% are reported in tis setting. Irinotecan is supplied without costs from the company Pfizer.

Metastatic gastric cancer, progressive disease after one palliative chemotherapy

Arm A:

Irinotecan 250/350 mg/m2 q3w

1. Cycle:250mg/m2/ 30min
2. Cycle:If no toxicity>2° CTC, nor Leuko-thrombopenia>3° occured, dose is increased to 350mg/m2 Arm B. Best supportive care

Inclusion Criteria:

• Patient with histologically proven adenocarcinoma of stomach or the gastro-esophageal junction
• Patient with distant metastases laparoscopically proven operative incurability of an locally advanced gastric cancer or patient with a tumor recurrence after gastrectomy
• Patient with progressive disease under a palliative first-line chemotherapy or progressive disease within 6 months after termination of a first-line chemotherapy, defined as objective progression by imaging techniques according to WHO criteria
• Age 18 and 75 years
• Sufficient liver function, defined as serum-bilirubin <1,5 mg/dl (1,5 upper normal limit), ALT und AST < 3x upper normal limit
• Sufficient renal function, defined as serum creatinine < 1,25 x upper normal limit or creatinine clearance >60ml/min calculated according to Crockroft-Gault
• Contraction for patient with reproductive potential
• Karnofsky-Index >60%
• Measurable or evaluable tumor manifestation

Exclusion Criteria:

• Tumor progression later than 6 months after termination of first-line chemotherapy
• KI 50% or less
• Patient who have already received a second line chemotherapy for the metastatic setting (adjuvant chemotherapy and one line of palliative chemotherapy os allowed, biologic prior therapies are allowed)
• Prior or current second malignancy despite of basal carcinoma of the skin and curatively treated carcinoma in situ of the cervix
• Uncontrolled infection
• CNS metastases
• Other severe medical illness
• Prior major surgery less than 2 weeks ago
• Parallel treatment with another experimental therapy
• Parallel treatment with another therapy aiming at tumor reduction
• Chronic diarrhea, subileus
• Chronic inflammatory bowel disease or intestinal obstruction
• Pretreatment with irinotecan