Cediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if Cediranib when added to chemotherapy is more effective than chemotherapy alone in prolonging life expectancy and slowing disease progression in patients with previously untreated metastatic colorectal cancer.

Official Title
-----------------
A Randomised, Double-blind, Phase III Study to Compare the Efficacy and Safety of Cediranib (AZD2171, RECENTIN™) When Added to 5 Fluorouracil, Leucovorin and Oxaliplatin (FOLFOX) or Capecitabine and Oxaliplatin (XELOX) With the Efficacy and Safety of Placebo When Added to FOLFOX or XELOX in Patients With Previously Untreated Metastatic Colorectal Cancer.

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

Intervention / Treatment
-----------------
* Drug: Cediranib
* Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)
* Drug: XELOX (Capecitabine and Oxaliplatin)
* Drug: Cediranib Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written Informed Consent Carcinoma of the colon or rectum One or more measurable lesions Exclusion Criteria: Adjuvant/neoadjuvant therapy within 6-12 months of study entry Untreated unstable brain or meningeal metastases Specific laboratory ranges Specific cardiovascular problems Participation in other trials within 30 days

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 |
| --- | --- |
| Placebo Comparator: FOLFOX + placebo Cediranib<br>FOLFOX + placebo Cediranib | Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)<br>* intravenous infusion<br>* Other names: Eloxatin®;Drug: Cediranib Placebo<br>* oral tablet<br>|
| Placebo Comparator: Xelox + placebo Cediranib<br>Xelox + placebo Cediranib | Drug: XELOX (Capecitabine and Oxaliplatin)<br>* intravenous oxaliplatin 130 mg/ m^2(day 1) followed by oral capecitabine 1,000 mg/ m^2twice daily (day 1 to day 15)<br>* Other names: Xeloda® + Eloxatin®;Drug: Cediranib Placebo<br>* oral tablet<br>|
| Experimental: FOLFOX + Cediranib<br>FOLFOX + Cediranib | Drug: Cediranib<br>* oral tablet<br>* Other names: RECENTIN™;Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)<br>* intravenous infusion<br>* Other names: Eloxatin®;|
| Experimental: XELOX + Cediranib<br>XELOX + Cediranib | Drug: Cediranib<br>* oral tablet<br>* Other names: RECENTIN™;Drug: XELOX (Capecitabine and Oxaliplatin)<br>* intravenous oxaliplatin 130 mg/ m^2(day 1) followed by oral capecitabine 1,000 mg/ m^2twice daily (day 1 to day 15)<br>* Other names: Xeloda® + Eloxatin®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | RECIST criteria defined as follows: Target lesions Complete Response (CR) Disappearance of all target lesions Partial Response (PR) At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD.Progressive Disease (PD) At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began).Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non-target lesions Complete Response (CR) Disappearance of all non-target lesions Non-Complete Response (non-CR/Non- Progression [non-PD]) Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing nontarget lesions. | RECIST assessed at baseline every 6 weeks through to week 24 and 12 week thereafter through to progression or data cut off date of 21/03/10 whichever was earliest. | 
| Overall Survival | Number of months from randomisation to the date of death from any cause | Baseline through to date of death upto and including data cut off date of 21/03/10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Objective tumour response(defined as a confirmed response of CR or PR).The definition for a confirmed response was met when an initial RECIST response of PR/CR was confirmed at the next scheduled visit as a PR/CR according to an evaluable assessment.Intervening assessments of non-evaluable or stable disease were allowable as long as the initial RECIST response was confirmed.RECIST criteria defined as follows: Target lesions Complete Response(CR)Disappearance of all target lesions Partial Response (PR).At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began).Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Non-target lesions Complete Response (CR) Disappearance of all non-target lesi | Baseline through to date of death upto and including data cut off date of 21/03/10 | 
| Best Percentage Change in Tumour Size | Maximum percentage reduction or minimum percentage increase in tumour size where size is the sum of the longest diameters of the target lesions | Baseline through to date of death upto and including data cut off date of 21/03/10 | 
| Duration of Response | Based on RECIST measurements taken throughout the study and best objective tumour response at the defined analysis cut-off point. Measured from the time the criteria for CR/PR are first met (whichever is recorded first) until the patient progresses or dies. | Treatment period from initial response up until data cut-off date of 21/03/10 | 
| Rate of Resection of Liver Metastases | Number of patients undergoing liver resection, based on patients with liver disease at baseline | Post-randomisation until end of study | 
| Time to Wound Healing Complications | Number of days from post-randomisation surgery until wound healing complications | Post-randomisation until end of study | 

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