A Phase I/II Study of Cediranib (AZD2171) in Japanese Metastatic Colorectal Cancer Patients in Combination With FOLFOX

Study Overview
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Brief Summary
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This Study is in two parts, the first part is to make sure that combining a potential new treatment, cediranib (AZD2171), with a standard treatment (FOLFOX) for metastatic colorectal cancer is safe. Once this part is complete and it is decided that it is safe to continue the Study will the go on to look at the efficacy of the two drugs together. This will be done by studying two treatment options. One will be the standard treatment alone (FOLFOX) + dummy cediranib (AZD2171) tablets and the other will be the standard treatment (FOLFOX) + real cediranib (AZD2171) tablets. Using dummy tablets means the study is 'blinded' and that non-one can tell the difference between the two treatment groups. This kind of study design is done to try to avoid the chance that the results might be biased in some way. The overall aim of the second part of the study is to see if adding cediranib (AZD2171) to a standard treatment for Metastatic Colorectal Cancer (mCRC), in this case FOLFOX, gives better results. That is, it's better than giving standard treatment alone in helping to prevent progression of mCRC.

Official Title
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A Two Part Study in Japanese Patients With mCRC, Consisting of an Open-label Phase I Part to Assess the Safety and Tolerability of Cediranib (AZD2171) in Combination With FOLFOX Followed by a Phase II, Randomised, Double-blind, Parallel Group Study to Assess the Efficacy of Cediranib (AZD2171) in Combination With FOLFOX

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: AZD2171
* Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)
* Drug: Placebo Cediranib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic colorectal cancer WHO performance status 0-1 Life expectancy is 12 weeks or longer Exclusion Criteria: Patient with uncontrolled brain metastases Patient with inappropriate laboratory tests values Patient with poorly controlled hypertension

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FOLFOX + Cediranib 20 mg<br>FOLFOX + Cediranib 20 mg | Drug: AZD2171<br>* oral tablet<br>* Other names: RECENTIN™;Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)<br>* intravenous infusion<br>* Other names: Leucovorin;|
| Active Comparator: FOLFOX + Cediranib 30 mg<br>FOLFOX + Cediranib 30 mg | Drug: AZD2171<br>* oral tablet<br>* Other names: RECENTIN™;Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)<br>* intravenous infusion<br>* Other names: Leucovorin;|
| Placebo Comparator: FOLFOX + Placebo Cediranib<br>FOLFOX + Placebo Cediranib | Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)<br>* intravenous infusion<br>* Other names: Leucovorin;Drug: Placebo Cediranib<br>* oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | 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. | RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumour Response Rate | Number of patients with complete (CR) /partial response (PR) (based on RECIST). CR is defined as Disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of Longest Diameter (LD) of target lesions taking as reference the baseline sum LD. | RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups) | 
| Best Percentage Change in Tumour Size | Best percentage change in tumour size from baseline, based on the sum of the longest diameters of the target lesions | Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups) | 
| Duration of Response | Number of months from Complete/Partial response until progression up to cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups). | RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups) | 
| Overall Survival | Number of months until death (censored if still alive at date cut-off). Median non-estimable if >50% of subjects within a group are censored. | Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Recentin, Metastatic Cancer, FOLFOX