Safety and Efficacy Study to Compare Capecitabine + Bevacizumab Versus Capecitabine, Concomitantly With Radiotherapy as Neoadjuvant Treatment for Patients With Localized and Resectable Rectal Cancer

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of the combination of capecitabine + bevacizumab concomitantly with radiotherapy versus capecitabine concomitantly with radiotherapy, as neoadjuvant treatment for patients with localized and resectable rectal cancer.

Official Title
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Phase II Randomized Study to Compare Capecitabine + Bevacizumab Concomitantly With Radiotherapy Versus Capecitabine Concomitantly With Radiotherapy, as Neoadjuvant Treatment for Patients With Localized and Resectable Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Bevacizumab + Capecitabine + Radiotherapy
* Drug: Capecitabine + Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age ≥18 years ECOG ≤ 1 Histologically confirmed carcinoma of the rectum Localized and resectable rectal cancer No metastatic disease Measurable disease Life expectancy more than 4 months Non prior treatment for rectal cancer Adequate haematological function: leu ≥ 4x 109 /l, Hb ≥10 gr/dl, neutropils≥ 1,5 x 109 /l and platelets ≥100 x 109 /l Adequate renal function: creatinine ≤ 106 umol/l or calculated creatinine clearance > 50 mL/min Adequate liver function: AST, ALT and alkaline phosphatase ≤2.5 x UL, bilirubin ≤1.5 x UL Adequate nutritional weight loss <10% of regular weight and albumin ≥ 35 g/l Exclusion Criteria: Unresectable rectal cancer Past or current history (within the last 5 years prior to treatment start) of other malignancies. Patients of childbearing potential not willing to use effective means of contraception. Clinically significant cardiovascular disease Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication. Patients subjected to organ allografts who require immunosuppressive treatment. Severe, non-cicatrized osseous fractures, wounds or ulcers. Indications of hemorrhagic diathesis or coagulopathy. Severe, uncontrolled intercurrent infections or other severe, uncontrolled concomitant diseases. History of unexpected severe reactions to treatment with fluoropyrimidines or known deficiency dihydropyrimidine dehydrogenase deficiency (DPD). Patients subjected to a major surgical procedure, open biopsy or who have had significant traumatic lesions within the 28 days prior to beginning the treatment of the study or in whom it is foreseen that a major surgical procedure will be necessary during the course of the study; fine-needle aspiration within the 7 days prior to beginning the treatment of the study. Current or recent use (within the 10 days prior to beginning the treatment of the study) of oral or parenteral anticoagulants at complete doses or thrombolytic agents. The use of low doses of warfarin is allowed, with an International Normalized Ratio [INR] of < 1.5. Daily chronic treatment with high doses of aspirin (> 325 mg/day) or non-steroid anti-inflammatory medications (which inhibit the platelet function at doses used for treating chronic inflammatory diseases). Patients who have received any drug or agent/procedure under research, i.e., who have participated in another clinical trial during the 4 weeks prior to beginning the treatment with the medications of the study Any psychological, familiar conditions suggesting that the patient will not be able to complete the study

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Bevacizumab + Capecitabine + Radiotherapy | Drug: Bevacizumab + Capecitabine + Radiotherapy<br>* Bevacizumab (5 mg/kg; days 1, 15 and 29) Capecitabine (825 mg/m2/12h, 5 days/w) Radiotherapy (45 Gy in sessions of 1.8 Gy 5 times/w for 5 weeks)<br>|
| Active Comparator: B<br>Capecitabine + Radiotherapy | Drug: Capecitabine + Radiotherapy<br>* Capecitabine (825 mg/m2/12h, 5 days/w) and Radiotherapy (45 Gy in sessions of 1.8 Gy 5 times/w for 5 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate complete pathologic responses |  | 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival at 3 and 5 years |  | 78 months | 
| Rate of local and distant recurrence at 3 and 5 years |  | 78 months | 
| Overall survival at 3 and 5 years |  | 78 months | 
| R0 resection rate. |  | 17 months | 
| Adverse events |  | 17 months | 
| Rate of surgery complications |  | 17 months | 
| Molecular predictive markers: changes in angiogenic parameters, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptors, microvessel quantification and angiopoietin-2 (Ang-2) |  | 17 months | 
| Rate of sphincter preservation |  | 17 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resectable rectal cancer, Radiotherapy, Bevacizumab, Capecitabine