Xeloda and Bevacizumab to Treat Rectal Cancer

Study Overview
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Brief Summary
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The project objective is to evaluate the efficacy of the neoadjuvant treatment with bevacizumab, capecitabine and radiotherapy, in patients with rectal adenocarcinoma resectable locally advanced (stage T3 or T4), with or without presence of ganglionar metastases and without distant metastases.

Official Title
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ESTUDIO FASE II DE BEVACIZUMAB EN COMBINACIÓN CON CAPECITABINA Y RADIOTERAPIA COMO TRATAMIENTO PREOPERATORIO EN PACIENTES CON CÁNCER RECTAL LOCALMENTE AVANZADO RESECABLE

Conditions
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Rectal Cancer

Intervention / Treatment
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* Biological: Bevacizumab
* Drug: capecitabine (Xeloda)
* Radiation: Rectal Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has given written informed consent prior to any study related procedure Male and female aged 18 to 75 years ECOG performance status 0 or 1 Histologically confirmed diagnostic of adenocarcinoma of the rectum < 15 cm from anal verge Clinical stage of T3, T4 with/without regional lymph node metastases, without metastatic disease Disease evaluable by imaging techniques No tumour haemorrhage in the week prior to start of study treatment External derivation in symptomatic occlusive tumours Not prior cancer treatment Adequate bone marrow, hepatic and renal function, defined as: White blood cells ≥ 4 x 109 /l Absolute neutrophil count ≥ 1.5 x 109 /l Platelets ≥ 100 x 109 /l Haemoglobin ≥10 g/dl Bilirubin < 1.25 x upper limit of normal Aspartate transaminase and alanine transaminase < 2.5 x upper limit of normal Serum creatinine ≤ 106 µmol/l Less than 10% weight loss Exclusion Criteria: Rectal cancer no amenable to resection Any other malignancy which has been active or treated within the past 5 years , with the exception of in situ carcinoma of the cervix and non-melanoma skin lesions adequately treated Pregnant or breast-feeding women Women oh childbearing potential unless effective methods of contraception are used No prior or concurrent significant medical conditions, including any of the following: Cerebrovascular disease (including transient ischemic attack and stroke) within the past year Cardiovascular disease, including the following: Myocardial infarction within the past year Uncontrolled hypertension while receiving chronic medication Unstable angina New York Heart Association class II-IV congestive heart failure Serious cardiac arrhythmia requiring medication Major trauma within the past 28 days Serious nonhealing wound, ulcer, or bone fracture Evidence of bleeding diathesis or coagulopathy No lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication No 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 No known dihydropyrimidine dehydrogenase deficiency Major surgery in the 4 weeks prior to the start of study treatment No concurrent chronic, daily treatment with aspirin (> 325 mg/day) More than 10 days since prior use of full-dose oral or parenteral anticoagulants for therapeutic purposes No participation in another clinical trial with any investigational drug within 30 days prior to randomization or during study participation No other medical history or condition that, in the opinion of the investigator, would preclude study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Bevacizumab & capecitabine & radiotheraphy<br>Bevacizumab 4 cycles each 15 days, the first 10 mg/kg and the rest of cycles with 5 mg/kg. Radiotherapy 45 Gy starting on Bevacizumab 2nd cycle during 5 weeks, 1.8 Gy per day, 5 days at week. Capecitabine 900 mg/m2 two times a day concomitant during radiotherapy period. | Biological: Bevacizumab<br>* Bevacizumab 4 cycles each 15 days, the first 10 mg/kg and the rest of cycles with 5 mg/kg.<br>Drug: capecitabine (Xeloda)<br>* Capecitabine 900 mg/m2 two times a day concomitant during radiotherapy period<br>Radiation: Rectal Radiotherapy<br>* Radiotherapy in rectum 45 Gy starting on Bevacizumab 2nd cycle during 5 weeks, 1.8 Gy per day, 5 days at week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response rate. % patients with pathologic complete response (absence of tumoral cells in the resected piece) |  | Surgery date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall clinical response |  | Surgery date | 
| To determine the downstaging caused by treatment |  | Surgery date | 
| relapse free survival |  | Time of radiological evidence of relapse. | 
| Quantify the local control grade: R0 resections in surgery |  | Surgery date | 
| Local relapse and distant relapse rates |  | Relapse date | 
| To determine the security profile of this neoadjuvant treatment (radio- chemotherapy) |  | From date of register to surgery date | 
| Surgery complication rate |  | During surgery admission. | 
| To determine the angiogenic profile changes in tumour. |  | 15 days, 6 weeks and 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectum, adenocarcinoma, neoadjuvant, bevacizumab, capecitabine, radiotherapy, locally, advanced, resectable, resectable locally advanced adenocarcinoma of the rectum, xeberecto