preoperative combined radiochemo-molecular target therapy with capecitabine, bevacizumab, and radiotherapy

Conditions: Rectal Cancer

Summary: * feasibility and tolerance of preoperative therapy with bevacizumab in combination with capecitabine and radiotherapy for patients with locally advanced, locally operable rectal carcinoma * collection of response rate (t- and m-downstaging, pathological complete remission)

combined radiochemotherapy: therapy start: within 28 days after bioptical diagnosis radiotherapy: 5 x 5 days 1.8 gy radiotherapy; cummulative dose 45 gy chemotherapy: capecitabin 825mg/m² bid, on each radiation day during the first 4 weeks rctx molecular targeted therapy: bevacizumab 5 mg/kg body weight; day 1, 15, 29 operation due to tme adherence to a break of min. 42 to max. 56 days after the last application of bevacizumab

Eligibility criteria:
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: \ 50 ml/min (cockcroft and gault formula)), proteinuria: 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

Keywords: pilot study rectal carcinoma phase ii preoperative radiochemo molecular target therapy t3 abcsg tako r04 08