First Line Metastatic Colorectal Cancer Therapy in Combination With FOLFOX

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to see if Cediranib in combination with FOLFOX is effective in treating metastatic colorectal cancer and to see how it compares with Avastin (Bevacizumab) in combination with FOLFOX.

Official Title
-----------------
A Randomised, Double-blind, Multicentre Phase II/III Study to Compare the Efficacy of Cediranib (RECENTIN™, AZD2171) in Combination With 5-fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX), to the Efficacy of Bevacizumab in Combination With FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Cediranib
* Drug: Bevacizumab
* Drug: 5-fluorouracil ( in FOLFOX)
* Drug: Leucovorin (in FOLFOX)
* Drug: Oxaliplatin (in FOLFOX)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical Diagnosis of colon or rectal cancer No prior systemic therapy for metastatic disease. Any adjuvant/neoadjuvant oxaliplatin therapy must have been received >12 months prior to study entry and adjuvant/neoadjuvant 5-FU must have been received >6 months prior to study entry. Exclusion Criteria: Prior treatment with a VEGF Inhibitor, including bevacizumab and cediranib. Poorly controlled hypertension

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 130 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Bevacizumab + FOLFOX | Drug: Bevacizumab<br>* intravenous infusion<br>* Other names: Avastin®;Drug: 5-fluorouracil ( in FOLFOX)<br>* intravenous infusion<br>* Other names: 5-FU;Drug: Leucovorin (in FOLFOX)<br>* intravenous infusion<br>Drug: Oxaliplatin (in FOLFOX)<br>* intravenous infusion<br>* Other names: Eloxatin®;|
| Experimental: 2<br>Cediranib + FOLFOX | Drug: Cediranib<br>* oral tablet once daily<br>* Other names: AZD2171;Drug: 5-fluorouracil ( in FOLFOX)<br>* intravenous infusion<br>* Other names: 5-FU;Drug: Leucovorin (in FOLFOX)<br>* intravenous infusion<br>Drug: Oxaliplatin (in FOLFOX)<br>* intravenous infusion<br>* Other names: Eloxatin®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression is defined as the number of months from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression. | Baseline then at Weeks 8, 16, 24 and then every 12 weeks until progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Number of months from randomisation to the date of death from any cause | Randomisation until data cut-off | 
| Objective Response Rate | Objective response rate is Complete Response (CR) + Partial Response (PR) as defined below: CR = Disappearance of all target lesions. PR = At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs. | Up until data cut-off | 
| Duration of Response | Duration of Response is calculated as the time from the first recording of CR/PR until the patient progresses, regardless of whether the patient was still taking study medication. Only confirmed responses are included in the calculation. For patients who had not progressed, the end date used in the calculation of duration of response is the data cut-off date of 15th November 2009. | Up until data cut-off date of 15/11/2007 | 
| Percentage Change in Tumour Size | Percentage change in tumour size from baseline to first RECIST assessment (Week 8) ((Week 8 - baseline)/baseline)*100 | Baseline to Week 8 | 
| Time to Worsening of Health Related Quality of Life (QOL) Based on the FACT Colorectal Symptom Index (FCSI) | Time to worsening of symptoms, as measured by the FACT colorectal symptom index (FCSI), will be defined as the time when a sustained clinically important deterioration in the total score from the FCSI has been recorded. | Baseline through to data cut-off | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metastatic Colorectal Cancer, RECENTIN