XELOX+Bevacizumab Followed by Capecitabine+Bevacizumab+Radiotherapy as Neoadjuvant Treatment of Locally Advanced Rectal Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the pathological complete response rate of addition of bevacizumab to induction therapy (xelox) and concomitant treatment (capecitabine+radiotherapy), followed by surgery.

Official Title
-----------------
Treatment of Induction With XELOX-Bevacizumab in Locally Advanced Rectal Adenocarcinoma: Phase II Study

Conditions
-----------------
Rectal Neoplasms, Locally Advanced Rectal Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: bevacizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent from patients who are able to understand the study request Histologically confirmed diagnosis of locally advanced rectal adenocarcinoma; ≤12 cm from the anal margin; T3, operable T4 or TxN+ Karnofsky PS Index ≥ 70% Life expectancy > 6 months Adequate bone marrow, liver and renal function: ANC ≥ 1.5 x 10e9/l; Platelets ≥ 100 x 10e9/l; Hb ≥ 9g/dl; INR ≤ 1.5; Bilirubin ≤ 1.5 x ULN; ALT and/or AST ≤ 2.5 x ULN or ≤ 5 x ULN (in case of hepatic metastasis); Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN (in case of hepatic metastasis) or ≤ 10 x ULN (in case of bone metastasis); Creatinine clearance (Cockcroft-Gault) ≥ 30 ml/min or seric creatinine ≤ 1.5 x ULN Exclusion Criteria: Distant metastases; previous neoplasm during last 5 years or previous infiltrating neoplasm; previous treatment with radiotherapy or study drugs; recruited for other clinical trial in 4 weeks before study entry Surgery, open biopsy or traumatic injury in 4 weeks before study entry; fine-needle aspiration in 7 days before study entry; major surgery planned during study Previous heart disease or uncontrolled hypertension, previous hemorrhagic diathesis or coagulopathy; full-dose oral or parenteral anticoagulant or thrombolytic agent (low-dose warfarin is allowed, INR ≤ 1.5); chronic use of high-dose aspirin (<325mg/day) or non-steroidal anti-inflammatory treatment No integrity of the upper gastrointestinal tract, malabsorption syndrome or unable to take oral drugs Pregnant or lactating patients; SNC disease; allogeneic transplant with immunosuppressive drugs; bone fracture not healed, wound or severe ulcers; uncontrolled intercurrent severe infections; previous related-fluoropyrimide SAEs or DPD deficiency

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>-Induction treatment. 4 cycles (every 3 weeks) of bevacizumab (7,5mg/kg day 1) + oxaliplatin (130mg/m2 day 1) + capecitabine (1000mg/m2/12h days 1-14) -Concomitant (CT+RT) treatment (3 weeks later): bevacizumab (5mg/kg day 1 of 1st, 3th and 5th weeks) + capecitabine (825mg/m2/12h daily during radiotherapy treatment) + radiotherapy (45Gy (25fractions of 1,8Gy/day over 5weeks) followed by boost 5.4Gy (1,8Gy/day over 3days)) -Surgery (6-8 weeks after last bevacizumab dose) -Adjuvant treatment: It will be individual decision of each investigator, but it's recommended 4 cycles of XELOX (equal dose at induction treatment) | Drug: bevacizumab<br>* -Induction treatment. 4 cycles (every 3 weeks) of bevacizumab (7,5mg/kg day 1) + oxaliplatin (130mg/m2 day 1) + capecitabine (1000mg/m2/12h days 1-14) -Concomitant (CT+RT) treatment (3 weeks later): bevacizumab (5mg/kg day 1 of 1st, 3th and 5th weeks) + capecitabine (825mg/m2/12h daily during radiotherapy treatment) + radiotherapy (45Gy (25fractions of 1,8Gy/day over 5weeks) followed by boost 5.4Gy (1,8Gy/day over 3days)) -Surgery (6-8 weeks after last bevacizumab dose) -Adjuvant treatment: It will be individual decision of each investigator, but it's recommended 4 cycles of XELOX (equal dose at induction treatment)<br>* Other names: Avastin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate |  | after concomitant CT-RT treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Resection (R0) Rate |  | after surgery | 
| Disease Free Survival |  | from complete response to relapse or disease-related death | 
| Time to Failure Treatment |  | from first treatment dose to drop out of the study | 
| Metastatic or Local Recurrence |  | during study | 
| Toxicity Evaluation |  | during study | 
| Surgical Morbility |  | during surgery |