Preoporative Bevacizumab, Radiation Therapy, and XELOX Chemotherapy for Locally Advanced Nonmetastatic Rectal Cancer

Study Overview
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Brief Summary
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We presumed that the addition of a monoclonal antibody Bevacizumab into radiation therapy and combination chemotherapy could results in improved pathologic tumor regression grade (TRG) in locally advanced nonmetastatic rectal cancer.

Detailed Description
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Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Giving bevacizumab together with radiation therapy and combination chemotherapy before surgery may achieve promising improvements in pCR rates, we designed this Phase II study in patients with T3/4 or N1/2 loco-regionally advanced rectum cancer, to examine the efficacy and safety of the addition of bevacizumab to a regimen of capecitabine and oxaliplatin in combination with pre-operative radiation.

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Xeloda
* Drug: Oxaliplatin
* Drug: Bevacizumab
* Radiation: Radiation
* Procedure: surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the colon or rectum. T3 or T4 adenocarcinoma or node positive colorectal tumours. Appropriate staging investigations of the primary tumour, either endorectal ultrasound or pelvic MRI. Male or female aged 18 to 70. Have a performance status ECOG of 0 or 1. Have a life expectancy greater than 6 months. Adequate organ function and coagulation parameters as measured by: WBC > 4000/mm3, PLT > 100000/mm3, Hb > 10g/dL, ALT < 1.5X ULN, AST < 1.5X ULN, bilirubin < 1.5mg/dL Serum creatinine < 1.8mg/dL. Patient consent. Exclusion Criteria: Known to have clinical or radiological evidence of distant metastases. Evidence of intestinal obstruction (except for those after enterostomy). Patients with a past history of colorectal surgery (except for enterostomy), chemtherapy, radiation, biotherapy or targeted therapy. Pregnant woman OR women of childbearing potential with a positive pregnancy test at baseline or lactating. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. Patients with a past or current history (within last 5 years) of other malignancies, except for the indication under this study and curatively treated basal and squamous skin cancer or in-situ cancer of the cervix. Patients with mental disorder unable to complete the informed consent. Uncontrolled hypertension. Clinically significant (i.e. active) cardiovascular disease for example: cerebrovascular accidents (<=6 months), myocardial infarction (<= 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. Moderate or serious proteinuria. Known hypersensitivity against experimental drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single Arm<br>Neoadjuvant chemotherapy with XELOX: Xeloda, po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning; Oxaliplatin, iv, 130mg/m2, day 1; and Bevacizumab, iv, 7.5 mg/kg, day 1, during the first cycle (each cycle has 3 weeks). Followed by chemoradiotherapy, 50 Gy/25 fractions during 5 weeks plus 2 cycles XELOX and Bevacizumab: Xeloda, po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning; Oxaliplatin, iv, 100mg/m2, day 1; and Bevacizumab, iv, 7.5 mg/kg, day 1. 6-7 weeks from the last radiation therapy, Total Mesorectal Excision (TME) surgery will be performed. 3-4 weeks after operation, 3 cycles XELOX (the same as the neoadjuvant chemotherapy) and 2 cycles Xeloda (po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning) will be administered. | Drug: Xeloda<br>* po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning, 8 cycles<br>* Other names: Capecitabine;Drug: Oxaliplatin<br>* iv, 130mg/m2, day 1, 1 cycle during neoadjuvant chemotherapy and 3 cycles in adjuvant chemotherapy 100mg/m2, day 1, 2 cycles during concurrent chemoradiotherapy<br>Drug: Bevacizumab<br>* iv, 7.5 mg/kg, day 1, 3 cycles during neoadjuvant chemotherapy and concurrent chemoradiotherapy<br>* Other names: Avastin;Radiation: Radiation<br>* Intensity-modulated radiation therapy, 50 Gy/25 fractions during 5 weeks<br>Procedure: surgery<br>* Total Mesorectal Excision (TME)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pathologic tumor regression grade (TRG) |  | March 30, 2015 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-y overall survival |  | March 30, 2020 | 
| Occurence of toxicity |  | March 30, 2015 | 
| 5-y local relapse free survival |  | March 30, 2020 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bevacizumab, capecitabine, oxaliplatin, preoporative IMRT, Rectal Cancer