A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Endocrine Tumors of the Gastrointestinal Tract.

An Open Label Study to Evaluate the Effect of Avastin in Association With Chemotherapy on Progression-free Survival in Patients With Progressive Advanced/Metastatic Well-differentiated Digestive Endocrine Tumors of the Gastrointestinal Tract

This 2 arm study will assess the efficacy and safety of two systemic treatments including Avastin in patients with previously-untreated progressive locally advanced/metastatic well-differentiated digestive endocrine tumors. Patients with duodeno-pancreatic tumors (arm 1) will be treated with 5FU/streptozotocin iv (5FU 400mg/m2/d D1 to D5;streptozotocin 500mg/m2/d/iv D1 to D5;D1=D42) every 6 weeks, plus Avastin 7.5mg/kg iv every 3 weeks. Patients with gastrointestinal tract tumors (arm 2) will be treated with Xeloda 1000mg/m2 po bid D1 to D14 plus Avastin 7.5mg/kg iv D1=D21 every 3 weeks. The patients will be treated with chemotherapy for a minimum of 6 months, unless there is tumor progression and/or unacceptable toxicity. The anticipated time on study treatment is until disease progression or unacceptable toxicity, and the target sample size is <100 individuals.

Inclusion Criteria:

• adult patients, >=18 years of age;
• well-differentiated gastrointestinal tract endocrine tumors, or duodeno-pancreatic endocrine tumors;
• no previous anti-cancer therapy, other than surgery;
• progressive metastatic disease;
• >=1 measurable lesion.

Exclusion Criteria:

• abnormal cardiac function, with history of ischemic heart disease in past 6 months and/or abnormal 12 lead ECG;
• patients with known bleeding disorders;
• unstable systemic disease;
• chronic daily treatment with high-dose aspirin, NSAIDs or corticosteroids;
• previous history of malignancy (other than successfully treated basal and squamous cell cancer of the skin, and/or in situ cancer of the cervix).