Preoperative Radiotherapy With Capecitabine and Bevacizumab in Locally Advanced Rectal Cancer: CRAB Phase II Study (CRAB)

Inclusion Criteria:

• Male or female patients with histologically proven adenocarcinoma of the rectum (tumour located below the peritoneum), T3/4 or any node positive disease (clinical stage according the TNM classification system)
• No evidence of metastatic disease.
• The disease must be considered either resectable at the time of entry or thought to become resectable after preoperative chemoradiation.
• Age 18 - 80 years
• WHO Performance Status 0-2
• No prior radiotherapy, chemotherapy or any targeting therapy for rectal cancer
• Adequate hematological, hepatic and renal function Ability to swallow tablets
• Signed informed consent
• Patients must be willing and able to comply with the protocol for duration of the study

Exclusion Criteria:

• Malignancy of the rectum other than adenocarcinoma
• Any unrested synchronous colon cancer
• Other co-existing malignancy or malignancy within the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin
• Significant heart disease (uncontrolled hypertension despite of medication (> 150/100 mmHg), NYHA class III or IV heart disease,unstable angina or myocardial infarction within the past 1 year prior the study entry, history of significant ventricular arrhythmia requiring treatment)
• Serious, non-healing wound, ulcer or bone fracture
• Evidence of active peptic ulcer or upper GI bleeding
• Evidence of bleeding diathesis or coagulopathy
• Chronic daily treatment with high-dose aspirin(>325mg/day)
• Current or recent (>10 days) use of full-dose of parenteral anticoagulants or thrombolytic agents for therapeutic purpose
• Patients receiving a concomitant treatment with drugs interacting with capecitabine such as flucitosine, phenytoin, or warfarin
• Known dihydropyrimidine dehydrogenase (DPD)deficiency
• Major surgery within 4 weeks prior to study treatment starts, or lack of complete recovery from the effects of major surgery or open biopsy
• Known hypersensitivity to biological drugs
• Treatment with any investigational drug within 30 days before beginning treatment with the study drug
• Pregnant or lactating patient
• Females with a positive or no pregnancy test unless childbearing potential can be otherwise excluded (amenorrheic for at least 2 years,hysterectomy or oophorectomy)