A Study of Avastin (Bevacizumab) in Patients With Newly Diagnosed Locally Advanced Rectal Cancer.

This study will assess the efficacy and safety of two different neoadjuvant treatment approaches including Avastin in newly diagnosed patients with high risk locally advanced rectal cancer. Patients will be randomized into one of two treatment arms. Arm A will undergo an induction phase, consisting of 6 cycles of Avastin (5mg/kg iv) plus FOLFOX 4, followed by a 7 week chemoradiation phase, consisting of Avastin (5mg/kg iv) plus 5-FU plus radiotherapy, followed by surgery. Arm B will omit the induction phase, but will undergo the chemoradiation phase followed by surgery. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

• Drug: bevacizumab [Avastin]
  6x2 week cycles of 5mg/kg iv + FOLFOX, followed by 4x2 week cycles of 5mg/kg iv + 5-FU + radiotherapy
• Drug: bevacizumab [Avastin]
  4 x 2 week cycles of 5mg/kg iv + 5-FU + radiotherapy

• Experimental: 1
  Intervention: Drug: bevacizumab [Avastin]
• Experimental: 2
  Intervention: Drug: bevacizumab [Avastin]

Inclusion Criteria:

• adult patients, 18-75 years of age;
• histologically confirmed locally advanced rectal cancer;
• measurable disease;
• ECOG performance status 0-1;
• no prior chemotherapy or radiation therapy for rectal cancer.

Exclusion Criteria:

• prior treatment with Avastin;
• prior radiotherapy to pelvic region, or previous cytotoxic chemotherapy;
• previous history of malignancy (other than basal and squamous cell cancer of the skin, or in situ cancer of the cervix);
• history or evidence of CNS disease;
• clinically significant cardiovascular disease;
• chronic treatment with high dose aspirin (>325mg/day) or NSAID.