Preoperative Combined RadioChemo-MolecularTargetTherapy of the Locally Advanced Rectum Carcinoma (cT3NxM0) - a Phase II Pilot Study With Preoperative Application of Capecitabine, Bevacizumab and Radiotherapy (RTx)
Inclusion Criteria:
- age: 18 - 80
- bioptical confirmed adenocarcinoma of the rectum in T3NxM0 status. The tumor has to
be basically surgically complete resectable (->R0).
- no former chemotherapy, radiotherapy of pelvis or abdomen and/or tumor resection of
rectum carcinoma
- WHO performance status 0-2
- adequate bone marrow reserve (granulocytes >= 3.000/µl, absolute neutrophil >= 0 1,5
x 10 9/l thrombocytes: >= 100.000/µl, haemoglobin >= 10g/dl)
- adequate hepatic function (Bilirubin: <= 1.5 x ULN, GOT und GPT <= 2.5 x ULN)
- adequate renal function (creatinin: <= 1.25 mg/dl, creatinin-clearance: > 50 ml/min
(Cockcroft and Gault formula)), proteinuria: dipstick < 2+. In case of dipstick > 2+
protein has to be measured in 24h urine and does not exceed more than 1g/24h)
- ability of intake of pills
- women of childbearing potential: exclusion of pregnancy (negative urin or serum
pregnancy test)
- willingness of women of childbearing potential and accordingly of potent men to use
approved contraceptives (e.g. birth-control pill, loop, condom) during and at least 3
month after conclusion of the study
- life expectancy of at least 3 month
- INR and aPTT < 1.5 ULN
- signed Informed Consent before recruitment
Exclusion Criteria:
- failure of one inclusion criteria
- former radiotherapy of pelvis or abdomen
- former chemotherapy
- any other kind of malign tumor in the last 5 years
- any other kind of tumour in the last 5 years with exception of basal cell carcinoma
of skin and cervix carcinoma in situ
- general contraindication or known hypersensitivity against Bevacizumab and/or
Capecitabine
- non malign disease, if there is a contraindication with radiotherapy, or chemotherapy
with Bevacizumab and Capecitabine, or a resection of rectum: uncontrolled
hypertension (systolic > 150 mmHG and/or diastolic >100 mmHG) or clinical significant
(e.g. active) cardiovascular disease: CVA (cardiovascular accident)/ cerebral
apoplexy (< 6 months before recruitment), myocardial infarct (< 6 months before
recruitment), instable angina pectoris, CHF with NYHA status II or higher, or treated
serious arrhythmia, hepatic disease, significant neurologic or psychiatric disorders
- florid, serious infections at the time of recruitment
- peripheral neuropathy (NCI CTC >= Grade 1)
- legally limited contractual capability or evidence of neurological or psychiatric
disease, if it will constrict the patients compliance in the opinion of the
investigator
- evidence of lacking cooperation of the patient
- major intervention within 28 days before recruitment, open wounds
- serious injuries, unhealed wounds or fractures
- patients with spinal compressions or metastases in central nervous system
- evidence of bleeding diathesis or coagulation dysfunction
- actual intake of anticoagulant or thrombolytic agents, Aspirin > 325 mg/d or within
10 days before study start)
- actual or recent (within 10 days before recruitment) therapeutic therapy with
fully-dosed anticoagulants. A prophylactic treatment is permitted.
- previous thromboembolic or hemorrhagic events within the last 6 months before
recruitment
- previous abdominal fistulas, GI perforation or intra-abdominal abscess within the
last 6 months
- treatment with other study medication within 28 days before recruitment
- patients with malabsorption syndrome or difficulties swallowing
- pregnant or breast feeding women