Phase II Study of Preoperative IMRT Combined With Capecitabine and Bevacizumab in Locally Advanced Rectal Cancer

Study Overview
=================
Brief Summary
-----------------
Pathological complete response, (pCR) correlates with a favourable overall prognosis in locally advanced rectal cancer patients underwent preoperative chemoradiation, so obtaining a pCR might be beneficial. The aim of the study is to investigate safety and efficacy of preoperative IMRT combined with bevacizumab and capecitabine. primary endpoint is pathological complete remission rate.

Official Title
-----------------
Phase II Study of Preoperative IMRT Combined With Capecitabine and Bevacizumab in Locally Advanced Rectal Cancer

Conditions
-----------------
Locally Advanced Malignant Neoplasm

Intervention / Treatment
-----------------
* Radiation: chemoradiation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients with histologically proven adenocarcinoma of the rectum ,T3/4 or any node positive disease (clinical stage according the TNM classification system) No evidence of metastatic disease. Age 18 - 65 years Kps 80-100 No prior radiotherapy, chemotherapy or any targeting therapy for rectal cancer Normal hematological, hepatic and renal function, Ability to swallow tablets Signed informed consent Patients must be willing and able to comply with the protocol for duration of the study Exclusion Criteria: Malignancy of the rectum other than adenocarcinoma Other co-existing malignancy or malignancy within the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin Significant heart disease (uncontrolled hypertension despite of medication (> 150/100 mmHg), NYHA class III or IV heart disease,unstable angina or myocardial infarction within the past 1 year prior the study entry, history of significant ventricular arrhythmia requiring treatment) Evidence of active peptic ulcer or upper GI bleeding Evidence of bleeding diathesis or coagulopathy Patients receiving a concomitant treatment with drugs interacting with capecitabine such as flucitosine, phenytoin, or warfarin Known hypersensitivity to biological drugs Treatment with any investigational drug within 30 days before beginning treatment with the study drug Pregnant or lactating patient

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: preoperative chemoradiation<br>radiotherapy: 50 Gy to the pelvis (25x 2 Gy on days 1-35, excluding weekends) .IMRT planing and technique with high energy photons will be used. All fields will be treated daily. Multileaf collimators will be used to shape individual radiation fields. Patients will be irradiated in a prone position with a full bladder and by using belly board to minimize exposure of the small bowel. capecitabine 825 mg/m² p.o. twice daily on days 1-35 (including weekends), bevacizumab: at dose 5 mg/kg on days -1, 15,31. Radical surgery (TME): to be undertaken ideally 6-8 weeks following completion of chemoradiation. | Radiation: chemoradiation<br>* radiotherapy: 50 Gy to the pelvis (25x 2 Gy on days 1-35, excluding weekends) .IMRT planing and technique with high energy photons will be used. All fields will be treated daily. Multileaf collimators will be used to shape individual radiation fields. Patients will be irradiated in a prone position with a full bladder and by using belly board to minimize exposure of the small bowel. capecitabine 825 mg/m² p.o. twice daily on days 1-35 (including weekends), bevacizumab: at dose 5 mg/kg on days -1, 15, 31. Radical surgery (TME): to be undertaken ideally 6-8 weeks following completion of chemoradiation.<br>* Other names: Preoperative Radiotherapy With Capecitabine and Bevacizumab;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete remission rate (pCR) | A TME surgery will be done 6-8 weeks after concurrent chemoradiation, pathological examination of surgical speciments will be show Pathological complete remission rate (pCR) | after pathological examination of surgical speciments (6-8 weeks after chemoradiation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and late toxicity | Acute toxicities will be assessed every week during chemoradiation period , one week before surgery(6 weeks after chemoradiation) and every 3 months after surgery for 2 years. late toxicites will be assessed every 6 months from the third year after surgery. | Toxicity/safety:during preoperative treatment, early and late postoperative follow up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preoperative Chemoradiotherapy, Bevacizumab, Locally Advanced Rectal Cancer