This phase II study will evaluate the effect of bevacizumab, capecitabine and oxaliplatin with radiation on rectal cancer. Researchers will also evaluate the tolerability (how it makes the patient feel) and safety of this combination by watching for harmful side-effects.It is hoped that by adding bevacizumab to the capecitabine/oxaliplatin treatment in combination with radiation before surgery will improve response rate.

Improved pre-operative therapy is required in the management of high risk rectal cancer in order to decrease local recurrence and increase the rate of sphincter sparing surgery. Capecitabine, oxaliplatin and bevacizumab represent new systemic agents and have been given safely in phase I and II trials concurrently with radiation with promising improvements in pCR rates of 15 -24% compared to historic rates of 8-14% achieved with 5-FU alone. Improvements in pCR rates have not been associated with an increase in post-operative complication rates. A trial of all three of these agents is justified due to their enhanced efficacy when given in combination as well as their non-overlapping treatment toxicity profile.

This is a one-armed, multi-centred, Phase II study in patients with T3/4 locally advanced and T3/4 low lying rectal cancer, to study the efficacy and safety of the addition of bevacizumab to a regimen of capecitabine and oxaliplatin in combination with pre-operative radiation.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the rectum, defined as either:

Mid- or upper rectal tumours (>= 6 - 15 cm): T3 or T4 adenocarcinoma that is fixed or partially fixed or tethered and is potentially resectable; or Low rectal tumours (<6cm): T3 or T4 adenocarcinoma: or Node positive rectal tumours (<= 15cm): T1-4N2 or T1-4N+ where pelvic nodes approach or invade the mesorectum.

M0/X or M1 is permitted as long as definitive resection of the primary tumour is planned and, in the opinion of the investigator, it is safe to delay full dose of systemic chemotherapy

• Appropriate staging investigations of the primary tumour, either endorectal ultrasound or pelvic MRI.
• Male or female aged 18 or older.
• Have a performance status ECOG of 0 or 1.
• Have a life expectancy greater than 6 months.
• Adequate organ function and coagulation parameters as measured by:

ANC >=1.5 platelets >=100 Serum creatinine <= 1.5X ULN AST, ALT <= 2.5X ULN Bilirubin <= 1.5 ULN PTT and INR within normal limits Albumin >= than 30

• Patient consent
• No neurological diseases that can increase the neurotoxicity of oxaliplatin
• Be willing and able to comply with the protocol for the duration of the study.

Exclusion Criteria:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day -14, (i.e. patients must have recovered from any major surgery), or anticipation of need for major surgical procedure during or within 7 weeks after chemo-radiotherapy.
• Known to have clinical or radiological evidence of CNS metastases.
• Patients with a past or current history (within last 2 years) of other malignancies, except for the indication under this study and curatively treated basal and squamous skin cancer or in-situ cancer of the cervix.
• Women of childbearing potential with either a positive or no pregnancy test at baseline or lactating. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. Patients of childbearing potential must be willing to use a reliable method of birth control. i.e.: doublebarrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device or tubal ligation during the study
• Evidence of bleeding diathesis or coagulopathy.
• Uncontrolled hypertension, defined as SBP > 150/100 on more than one occasion that does not respond to therapy with antihypertensive agents
• Clinically significant (i.e. active) cardiovascular disease for example:

cerebrovascular accidents (<=6 months), myocardial infarction (<= 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.

• Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes i.e. except for anticoagulation for maintenance of patency of permanent indwelling IV catheters.
• Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or puts the patient at high risk from treatment complications.
• Ongoing treatment with aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration.
• Any other serious or uncontrolled illnesses.
• Current or recent serious polyneuropathy.
• Known hypersensitivity against bevacizumab.
• Known peripheral neuropathy >= NCI CTCAE grade 1. Absence of deep tendon reflexes (DTRs) as the sole neurologic abnormality does not render the patient ineligible.
• Organ allografts requiring immunosuppressive therapy.
• Serious, non-healing wound, ulcer, or bone fracture.