Advanced Breast Cancer
Conditions
Keywords
Advanced Breast Cancer
Brief summary
The purpose of this study is to determine whether AZD2171 can effectively improve time to tumour progression when added to fulvestrant in patients with advanced hormone sensitive breast cancer who progressed on prior hormonal therapy.
Interventions
DRUGAZD2171
Oral tablet
DRUGFulvestrant
intramuscular injection
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Females with histological/cytological confirmation of hormone sensitive breast cancer with evidence of metastatic disease * One or more evaluable lesions
Exclusion criteria
* Prior hormonal therapy with fulvestrant * More than one course of prior systemic cytotoxic chemotherapy for metastatic breast cancer * Prior biologic therapy for ABC including Anti-VEGF agents * Radiation therapy within 4 weeks prior to provision of consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest. | 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 Response Rate | RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest. | Best objective tumour response (based on Response Evaluation Criteria in Solid Tumours (RECIST)) during the study for patients with measurable disease. Best objective tumour response defined as: Complete Response (CR) Disappearance of all target lesions Partial response (PR) At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs. Progression (PD) At least a 20% increase in the sum of LDs of target lesions, taking as reference the smallest sum of LDs since treatment started (including the baseline sum of LDs) and at least 5 mm increase. Stable disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD |
| Duration of Response | Every 8 weeks until progression or discontinuation | Number of days from date of response (complete/partial based on RECIST) to date of progression |
| Clinical Benefit Rate | Every 8 weeks until progression or discontinuation | Clinical Benefit is defined as the number of patients having a best overall tumour response of CR/PR or SD for ≥6 months. The Clinical Benefit rate is defined as the number of responders divided by the number in the Intention-to-treat (ITT) analysis set: responder=overall best response of complete response (CR)/partial response (PR) or stable disease (SD) for at least 6 months (calculated from the date of randomisation) as defined by RECIST criteria at any point prior to the data cut-off. |
| Duration of Clinical Benefit | Every 8 weeks until progression or discontinuation | Number of days from date of clinical benefit to date of progression. Clinical benefit is defined as having a best overall tumour response of CR/PR or SD for ≥6 months. |
Countries
Australia, Brazil, United States
Participant flow
Recruitment details
Randomised=ITT=Safety: Cediranib 31, Placebo 31
Pre-assignment details
In this study, 75 patients were enrolled and 62 randomised.
Participants by arm
| Arm | Count |
|---|---|
| Cediranib 45 mg Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally) | 31 |
| Placebo Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally) | 31 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Disease progression | 16 | 19 |
| Overall Study | In order to begin radiotherapy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 2 |
Baseline characteristics
| Characteristic | Cediranib 45 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 11.4 | 57.9 Years STANDARD_DEVIATION 9.7 | 59.1 Years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 31 Participants | 31 Participants | 62 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 31 | 30 / 31 |
| serious Total, serious adverse events | 15 / 31 | 4 / 31 |
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 performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cediranib 45 mg | Progression Free Survival | 223 Days |
| Placebo | Progression Free Survival | 112 Days |
Secondary
Clinical Benefit Rate
Clinical Benefit is defined as the number of patients having a best overall tumour response of CR/PR or SD for ≥6 months. The Clinical Benefit rate is defined as the number of responders divided by the number in the Intention-to-treat (ITT) analysis set: responder=overall best response of complete response (CR)/partial response (PR) or stable disease (SD) for at least 6 months (calculated from the date of randomisation) as defined by RECIST criteria at any point prior to the data cut-off.
Time frame: Every 8 weeks until progression or discontinuation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cediranib 45 mg | Clinical Benefit Rate | 0.419 Ratio |
| Placebo | Clinical Benefit Rate | 0.419 Ratio |
Secondary
Duration of Clinical Benefit
Number of days from date of clinical benefit to date of progression. Clinical benefit is defined as having a best overall tumour response of CR/PR or SD for ≥6 months.
Time frame: Every 8 weeks until progression or discontinuation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cediranib 45 mg | Duration of Clinical Benefit | 306.6 Days | Standard Deviation 104.2 |
| Placebo | Duration of Clinical Benefit | 343.8 Days | Standard Deviation 115.8 |
Secondary
Duration of Response
Number of days from date of response (complete/partial based on RECIST) to date of progression
Time frame: Every 8 weeks until progression or discontinuation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cediranib 45 mg | Duration of Response | 207.5 Days |
| Placebo | Duration of Response | 224.0 Days |
Secondary
Objective Response Rate
Best objective tumour response (based on Response Evaluation Criteria in Solid Tumours (RECIST)) during the study for patients with measurable disease. Best objective tumour response defined as: Complete Response (CR) Disappearance of all target lesions Partial response (PR) At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs. Progression (PD) At least a 20% increase in the sum of LDs of target lesions, taking as reference the smallest sum of LDs since treatment started (including the baseline sum of LDs) and at least 5 mm increase. Stable disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
Time frame: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cediranib 45 mg | Objective Response Rate | 4 Participants |
| Placebo | Objective Response Rate | 1 Participants |