Advanced Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
oncology, cancer, breast cancer
Brief summary
This study will assess the relationship between fulvestrant dose and efficacy in postmenopausal women with oestrogen receptor positive advanced breast cancer.
Interventions
DRUGFulvestrant
intramuscular injection 250 mg & 500 mg
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Breast Cancer has continued to grow after having received treatment with an anti-estrogen hormonal treatment such as tamoxifen or an aromatase inhibitor. * Requiring hormonal treatment. * Postmenopausal women (woman who has stopped having menstrual periods)
Exclusion criteria
* Treatment with more than one previous regimen of systemic anticancer therapy other than endocrine therapy for advanced BC. * Treatment with more than one previous regimen of endocrine therapy for advanced BC. * An existing condition that prevents compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (ORR) | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | Objective response rate was defined as percentage of patients with either complete response (CR - disappearance of all target lesions) or partial response (PR - at least 30% decrease in the sum of diameters of target lesions). All patients were to be followed up every 12 weeks for progression, defined by response evaluation criteria in solid tumors (RECIST v1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | Time from randomisation until objective disease progression or death (in the absence of objective progression) using the Kaplan-Meier method. RECIST tumor assessments were carried out every 12 weeks until progression. |
| Duration of Response (DoR) | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | DoR was defined as the time from date of first documentation of the response (CR or PR) until the date of disease progression or death from any cause. |
| Clinical Benefit Rate (CBR) | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | CBR was defined as the proportion of all randomised patients who had clinical benefit (response of CR, PR or SD\>=24 weeks. |
| Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body | Baseline to 12 weeks | A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. |
| Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes | Baseline to 12 weeks | A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. The mean estimate of volume of distribution at steady state was reported as the sum of V1/F and V2/F in the clinical study report. |
Countries
Belgium, Canada, Czechia, France, Hungary, Poland, Romania, Turkey (Türkiye)
Participant flow
Recruitment details
Postmenopausal women with oestrogen receptor positive advanced breast cancer progressing or relapsing after previous endocrine therapy were randomised between 30th May 2006 and 30th November 2007
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant 250 mg Fulvestrant 250 mg | 47 |
| Fulvestrant 250 mg + Loading Dose Fulvestrant 250 mg + Loading Dose | 51 |
| Fulvestrant 500 mg Fulvestrant 500 mg | 46 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Death | 2 | 4 | 2 |
| Overall Study | Disease progression | 31 | 26 | 27 |
| Overall Study | Incorrect enrollment | 0 | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Progression (investigators opinion) | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Fulvestrant 250 mg | Fulvestrant 250 mg + Loading Dose | Fulvestrant 500 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 9.9 | 68.1 years STANDARD_DEVIATION 9.9 | 65.5 years STANDARD_DEVIATION 9 | 65.8 years STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Caucasian | 45 Participants | 51 Participants | 46 Participants | 142 Participants |
| Race/Ethnicity, Customized Oriental (Asian other than Chinese or Japanese) | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Oriental (Japanese) | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 47 Participants | 51 Participants | 46 Participants | 144 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 47 | 4 / 50 | 2 / 46 |
| other Total, other adverse events | 36 / 47 | 35 / 50 | 31 / 46 |
| serious Total, serious adverse events | 4 / 47 | 9 / 50 | 4 / 46 |
Outcome results
Primary
Objective Response (ORR)
Objective response rate was defined as percentage of patients with either complete response (CR - disappearance of all target lesions) or partial response (PR - at least 30% decrease in the sum of diameters of target lesions). All patients were to be followed up every 12 weeks for progression, defined by response evaluation criteria in solid tumors (RECIST v1.1).
Time frame: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | Objective Response (ORR) | 8.5 Percentage of patients |
| Fulvestrant 250 mg + Loading Dose | Objective Response (ORR) | 5.9 Percentage of patients |
| Fulvestrant 500 mg | Objective Response (ORR) | 15.2 Percentage of patients |
Secondary
Clinical Benefit Rate (CBR)
CBR was defined as the proportion of all randomised patients who had clinical benefit (response of CR, PR or SD\>=24 weeks.
Time frame: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | Clinical Benefit Rate (CBR) | 31.9 Percentage of patients |
| Fulvestrant 250 mg + Loading Dose | Clinical Benefit Rate (CBR) | 47.1 Percentage of patients |
| Fulvestrant 500 mg | Clinical Benefit Rate (CBR) | 47.8 Percentage of patients |
Secondary
Duration of Response (DoR)
DoR was defined as the time from date of first documentation of the response (CR or PR) until the date of disease progression or death from any cause.
Time frame: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.
Population: All objective responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 250 mg | Duration of Response (DoR) | NA Days |
| Fulvestrant 250 mg + Loading Dose | Duration of Response (DoR) | NA Days |
| Fulvestrant 500 mg | Duration of Response (DoR) | 539 Days |
Secondary
Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body
A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean.
Time frame: Baseline to 12 weeks
Population: Participants who had PK samples only
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant 250 mg | Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body | 31 litres per hour | Standard Error 3.29 |
Secondary
Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes
A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. The mean estimate of volume of distribution at steady state was reported as the sum of V1/F and V2/F in the clinical study report.
Time frame: Baseline to 12 weeks
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fulvestrant 250 mg | Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes | V1/F | 20600 Liters | Standard Error 3.67 |
| Fulvestrant 250 mg | Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes | V2/F | 35700 Liters | Standard Error 27.8 |
Secondary
Time to Progression (TTP)
Time from randomisation until objective disease progression or death (in the absence of objective progression) using the Kaplan-Meier method. RECIST tumor assessments were carried out every 12 weeks until progression.
Time frame: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 250 mg | Time to Progression (TTP) | 88 Days |
| Fulvestrant 250 mg + Loading Dose | Time to Progression (TTP) | 172 Days |
| Fulvestrant 500 mg | Time to Progression (TTP) | 169 Days |