Metastatic Colorectal Cancer
Conditions
Keywords
Colorectal cancer, Recentin, Metastatic Cancer, FOLFOX
Brief summary
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.
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumour Response Rate | 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) | 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. |
| Best Percentage Change in Tumour Size | Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups) | Best percentage change in tumour size from baseline, based on the sum of the longest diameters of the target lesions |
| Duration of Response | 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) | 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). |
| Overall Survival | Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups) | 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. |
Countries
Japan
Participant flow
Recruitment details
Randomised=ITT=Safety: Cediranib 20mg=58, Cediranib 30mg=56, Placebo=58
Pre-assignment details
PFS & OS: median based on Kaplan Meier analysis (i.e. adjusted for censored observations) but full range based on raw data (i.e. not adjusted for censored observations). OS: median non-estimable due to censored observations
Participants by arm
| Arm | Count |
|---|---|
| Cediranib 20 mg FOLFOX + Cediranib 20 mg | 58 |
| Cediranib 30 mg FOLFOX + Cediranib 30 mg | 56 |
| Placebo FOLFOX + Placebo | 58 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 15 | 9 | 14 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Cediranib 20 mg | Cediranib 30 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 62.4 years STANDARD_DEVIATION 9.3 | 62.1 years STANDARD_DEVIATION 9.9 | 62.2 years STANDARD_DEVIATION 9.6 | 62.2 years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 20 Participants | 26 Participants | 19 Participants | 65 Participants |
| Sex: Female, Male Male | 38 Participants | 30 Participants | 39 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 58 | 56 / 56 | 58 / 58 |
| serious Total, serious adverse events | 23 / 58 | 22 / 56 | 11 / 58 |
Outcome results
Primary
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.
Time frame: 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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cediranib 20 mg | Progression Free Survival | 10.23 Months |
| Cediranib 30 mg | Progression Free Survival | 8.85 Months |
| Placebo | Progression Free Survival | 8.32 Months |
Secondary
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
Time frame: Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cediranib 20 mg | Best Percentage Change in Tumour Size | -36.56 Percentage | Standard Deviation 24.52 |
| Cediranib 30 mg | Best Percentage Change in Tumour Size | -43.99 Percentage | Standard Deviation 22.62 |
| Placebo | Best Percentage Change in Tumour Size | -40.22 Percentage | Standard Deviation 35.84 |
Secondary
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).
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cediranib 20 mg | Duration of Response | 13.26 Months | Standard Deviation 16.81 |
| Cediranib 30 mg | Duration of Response | 8.12 Months | Standard Deviation 6.18 |
| Placebo | Duration of Response | 10.42 Months | Standard Deviation 10.97 |
Secondary
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.
Time frame: 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cediranib 20 mg | Objective Tumour Response Rate | 31 Participants |
| Cediranib 30 mg | Objective Tumour Response Rate | 39 Participants |
| Placebo | Objective Tumour Response Rate | 31 Participants |
Secondary
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.
Time frame: Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cediranib 20 mg | Overall Survival | NA Months |
| Cediranib 30 mg | Overall Survival | 20.07 Months |
| Placebo | Overall Survival | 19.51 Months |