Preoperative Combined Induction Chemotherapy With Capecitabine, Oxaliplatin, Bevacizumab and Radiotherapy

Inclusion Criteria:

* Age 18-80 years
* Histologic confirmation of rectal adenocarcinoma stage cT3 (≤ 5mm to the mesorectal fascia)/cT4( primary curative intention)NxM0
* No former chemotherapy, no former radiotherapy of the pelvic, no former tumour resection of a rectal carcinoma
* General condition WHO grade 0-2
* Adequate bone marrow reserve ( leucocytes ≥3 000/μl, thrombocytes ≥100 000/μl)
* Adequate renal function (creatinine ≤ 1,5 mg/dl, creatinine clearance \> 50ml/min (Cockcroft and Gault formula))
* Adequate liver function (bilirubin ≤1,5x ULN, GOT and GPT ≤3,5xULN)
* Exclusion of pregnancy for women with childbearing potential (negative pregnancy test urine or serum)
* Female patients with childbearing potential and male patients that are not surgically sterile must be practicing a medically acceptable contraceptive regimen while on study treatment until 3 months after the end of the study (e.g. oral contraceptives, condom, intrauterine device)
* Life expectancy of at least 3 months
* INR and aPTT ≤ 1,5 x LLN
* Provision of signed informed consents before registration

Exclusion Criteria:

* Rectal carcinoma stage cT3 (\> 5mm from the mesorectal fascia) all stages \<cT3, M1
* Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
* General contraindication or known hypersensitivity against Bevacizumab, Capecitabine and Oxaliplatin
* Not malignant diseases for which treatment with radiotherapy, resection of the rectum and treatment with chemotherapy (Bevacizumab, Capecitabine) is contraindicated: uncontrolled hypertension (systolic \> 150 mmHG and/or diastolic \> 100 mmHG) or clinically significant (e.g. active) cardiovascular diseases: CVA (cardiovascular accident)/ apoplectic insult (≤ 6 months prior to registration), myocardial infarction (≤ 6 months prior to registration), unstable angina pectoris, CHF(congestive heart failure) with NYHA (New York heart Association) Grade II or higher, cardiac arrhythmia requiring therapy, hepatic diseases, significant neurologic or psychiatric disorders
* Florid, serious infection at registration
* Peripheral neuropathy (NCI CTCAE v 4.0 ≥ grade 1)
* Juridically limited contractual capability, indication of neurological or psychiatric disease which constrains upon investigators opinion the patients capability to adhere to the study routines
* Major surgical procedure within 28 days prior start of the study, open wounds
* Significant traumatic injury, bone fracture, unhealed wounds
* Patients with spinal cord compression or metastases in the central nervous system
* Indication of bleeding diathesis or coagulopathy
* Intake of anticoagulant or thrombolytic agents and/or Aspirin \> 325 mg/d within 10 days prior to registration
* Current or recent (within 10 days prior to treatment start) therapy with full dosed anticoagulants. Preventive therapy is allowed.
* Previous thromboembolic or haemorrhagic events within 6 months prior to registration
* Previous abdominal fistulas, gastro-intestinal perforation or intrabdominal abscesses within 6 months prior to registration
* Treatment with another investigational drug within 28 days prior to registration
* Patients with malabsorption syndrome or difficulties in swallowing
* Indication of poor compliance of the patient
* Pregnant or breast-feeding women
* Proteinuria: Dipstick \<2+. If the Dipstick is ≥2+ protein has to be estimated in the 24 hours urine. The value should not be higher then 1g/24 hours.