Neoplasms, Breast Neoplasms, Breast Cancer
Conditions
Keywords
Cancer, tumour, breast cancer, metastatic, secondary, locally advanced
Brief summary
The main purpose of this study is to compare progression free survival in patients treated with AZD8931 given in combination with anastrozole versus anastrozole alone. The secondary objective is to investigate the safety and tolerability of AZD8931 given in combination with anastrozole.
Interventions
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patients that have locally advanced or metastatic breast cancer. Lesions should not be amenable to surgery or radiation of curative intent * Hormone therapy-naive * Estimated life expectancy of more than 12 weeks
Exclusion criteria
* Last dose of prior anti-cancer therapy received within 14 days (or longer if required) * Any eye injury or corneal surgery within 3 months prior to receiving first dose of study drug. * Currently receiving (and unwilling to discontinue) oestrogen replacement therapy. (last dose \<7 days prior to randomisation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | Tumour assessment by RECIST 1.1 every 12 weeks until data cut-off at 31 August 2012 | Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression). Disease progression is defined using RECIST 1.1 as \>=20% increase in the sum of longest diameters of target lesions and an absolute increase of \>=5mm, taking as reference the smallest sum of longest diameters of target lesions since study start, or unequivocal progression in non-target lesions, or appearance of any new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Overall Survival in Patients Treated With AZD8931 in Combination With Anastrozole Versus Anastrozole Alone | Following progression, patients were contacted at 12 weekly intervals until data cut-off at 31 August 2012 to determine survival status | Time from the date of randomization to the date of death (by any cause) |
Countries
Brazil, Canada, Czechia, Finland, India, Japan, Mexico, Peru, Philippines, Poland, Russia, South Africa, South Korea, Taiwan, Thailand, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
482 patients were enrolled into the study, of these, 123 patients failed screening and 359 patients were randomized, 120 to AZD8931 40mg(bd) plus anastrozole 1mg (od), 118 to AZD8931 20mg(bd) plus anastrozole 1mg (od) and 121 to placebo(bd) plus anastrozole 1mg(od)
Participants by arm
| Arm | Count |
|---|---|
| AZD8931 40mg + Anastrozole 1mg AZD8931 40mg (bd) plus anastrozole 1mg (od) | 120 |
| AZD8931 20mg + Anastrozole 1mg AZD8931 20mg (bd) plus anastrozole 1mg (od) | 118 |
| Placebo + Anastrozole 1mg Placebo (bd) plus anastrozole 1mg (od) | 121 |
| Total | 359 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 16 | 20 | 11 |
| Overall Study | Disease progression | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 3 |
| Overall Study | Safety as judged by the investigator | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 2 |
| Overall Study | Worsening of condition under study | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | AZD8931 40mg + Anastrozole 1mg | AZD8931 20mg + Anastrozole 1mg | Placebo + Anastrozole 1mg |
|---|---|---|---|---|
| Age, Continuous | 61.0 Years STANDARD_DEVIATION 10.73 | 60.4 Years STANDARD_DEVIATION 10.69 | 62.0 Years STANDARD_DEVIATION 11.23 | 60.5 Years STANDARD_DEVIATION 10.29 |
| Race/Ethnicity, Customized Ethnicity: African | 7 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Ethnicity: Asian (other than Chinese/Japanese) | 98 Participants | 35 Participants | 31 Participants | 32 Participants |
| Race/Ethnicity, Customized Ethnicity: Chinese | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 149 Participants | 51 Participants | 53 Participants | 45 Participants |
| Race/Ethnicity, Customized Ethnicity: Japanese | 8 Participants | 0 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity: Native American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity: Not applicable | 49 Participants | 19 Participants | 11 Participants | 19 Participants |
| Race/Ethnicity, Customized Ethnicity: Other | 46 Participants | 12 Participants | 17 Participants | 17 Participants |
| Race/Ethnicity, Customized Race: American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race: Asian | 108 Participants | 35 Participants | 37 Participants | 36 Participants |
| Race/Ethnicity, Customized Race: Black or African American | 18 Participants | 5 Participants | 7 Participants | 6 Participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race: Other | 67 Participants | 30 Participants | 18 Participants | 19 Participants |
| Race/Ethnicity, Customized Race: White | 166 Participants | 50 Participants | 56 Participants | 60 Participants |
| Sex/Gender, Customized | 359 Participants | 120 Participants | 118 Participants | 121 Participants |
| Study Stratification: Disease Classification Locally advanced | 83 Participants | 28 Participants | 27 Participants | 28 Participants |
| Study Stratification: Disease Classification Metastatic disease | 276 Participants | 92 Participants | 91 Participants | 93 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 | 112 / 118 | 115 / 120 | 99 / 121 |
| serious Total, serious adverse events | 14 / 118 | 17 / 120 | 11 / 121 |
Outcome results
Primary
Progression Free Survival as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression). Disease progression is defined using RECIST 1.1 as \>=20% increase in the sum of longest diameters of target lesions and an absolute increase of \>=5mm, taking as reference the smallest sum of longest diameters of target lesions since study start, or unequivocal progression in non-target lesions, or appearance of any new lesions.
Time frame: Tumour assessment by RECIST 1.1 every 12 weeks until data cut-off at 31 August 2012
Population: Full Analysis Set (all participants randomized, irrespective of whether treatment was received). Participants are analysed according to the treatment group they were randomized to.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD8931 40mg + Anastrozole 1mg | Progression Free Survival as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | 13.8 Months |
| AZD8931 20mg + Anastrozole 1mg | Progression Free Survival as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | 10.9 Months |
| Placebo + Anastrozole 1mg | Progression Free Survival as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | 14.0 Months |
Comparison: 345 patients were to be randomised to observe at least 233 progression events, based on HR=0.60, 90% power, 2-sided 5% significant level and a median of 9 months for the placebo arm. An interim analysis with futility boundary was introduced based on an IDMC recommendation.p-value: 0.48595% CI: [0.77, 1.75]Log Rank
Comparison: 345 patients were to be randomised to observe at least 233 progression events, based on HR=0.6, 90% power, 2-sided 5% significant level and a median of 9 months for the placebo arm. An interim analysis with futility boundary was introduced based on an IDMC recommendation.p-value: 0.13595% CI: [0.91, 2.06]Log Rank
Secondary
Compare the Overall Survival in Patients Treated With AZD8931 in Combination With Anastrozole Versus Anastrozole Alone
Time from the date of randomization to the date of death (by any cause)
Time frame: Following progression, patients were contacted at 12 weekly intervals until data cut-off at 31 August 2012 to determine survival status
Population: Full Analysis Set (all participants randomized, irrespective of whether treatment was received). Participants are analysed according to the treatment group they were randomized to.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD8931 40mg + Anastrozole 1mg | Compare the Overall Survival in Patients Treated With AZD8931 in Combination With Anastrozole Versus Anastrozole Alone | 6.9 Months |
| AZD8931 20mg + Anastrozole 1mg | Compare the Overall Survival in Patients Treated With AZD8931 in Combination With Anastrozole Versus Anastrozole Alone | 8.3 Months |
| Placebo + Anastrozole 1mg | Compare the Overall Survival in Patients Treated With AZD8931 in Combination With Anastrozole Versus Anastrozole Alone | 7.9 Months |