Preoperative Combined RadioChemo-Molecular Target Therapy With Capecitabine, Bevacizumab, and Radiotherapy

Study Overview
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Brief Summary
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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)

Detailed Description
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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

Official Title
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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)

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: capecitabine, bevacizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: capecitabine, bevacizumab<br>* Capecitabine 825 mg/m2 bid (on each therapy day of first 4 Therapy weeks) Bevacizumab 5 mg/kg weight; day 1, 15, 29<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility and tolerance of preoperative therapy with Bevacizumab in combination with Capecitabine and radiotherapy for patients with locally advanced, locally operable rectal carcinoma |  | descriptive evaluation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| collection of response rate (T- and M-downstaging, pathological complete remission) |  | descriptive evaluation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pilot study, rectal, carcinoma, phase II, preoperative, RadioChemo, molecular, target, therapy, T3, ABCSG, TAKO, R04, 08