Chemoradiation for Locally Advanced and Low Rectal Cancers: Avastin-Capecitabine-Oxaliplatin-Radiation REctal Cancer Trial

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.