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, and determine the dosing regimen as a second line therapy for Japanese postmenopausal women with oestrogen receptor positive advanced breast cancer.
Interventions
DRUGFulvestrant
250 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
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 defined as a 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 breast cancer * Treatment with more than one previous regimen of endocrine therapy for advanced breast cancer * An existing serious disease, illness, or condition that will prevent participation or compliance with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | baseline and every 12 weeks (+/- 2weeks) from randomization data up to data cut-off (19th march 2008) | An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response. Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | every 12 weeks from randomization (+/- 2 weeks) until data cut-off (19th march 2008) | Time (in days) from randomization until objective disease progression or death (in the absence of objective progression). RECIST tumour assessments carried out every 12 weeks from randomization (+/- 2 weeks) until data cut-off on 19th March 2008. |
| Duration of Response (DoR) | RECIST tumour assessments carried out every 12 weeks from randomisation (+/- 2 weeks) until data cut-off on19th March 2008. | Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieved a confirmed Complete Response or confirmed Partial Response. |
| Clinical Benefit Rate (CBR) | every 12 weeks(+/- 2 weeks) from randomization to data up to data cut-off, 19th March 2008. | A Clinical Benefit (CB) responder is defined as a patient having a best overall response of Complete response (CR), Partial Response (PR) or Stable disease (SD) provided SD (or better) was present = 154 days from randomization (ie SD = 24 weeks with the 2 week RECIST assessment time window allowed). The Clinical Benefit Rate is the percentage of patients with CB. |
| Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body | Baseline to 12 weeks | The measure of dispersion for mean population clearance is based on the estimated inter-individual variance |
| 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 | The measure of dispersion for volume of distribution is based on the inter-individual variance estimated for the apparent volume of plasma into which Fulvestrant distributes |
Countries
Japan
Participant flow
Recruitment details
Postmenopausal women with oestrogen receptor positive advanced breast cancer progressing or relapsing after previousendocrine therapy were randomized between 7th March 2006 and 4th September 2007. The trial was conducted in Japan only. One patient randomised to Fulvestrant 500mg was not dosed, so the Safety population has 46 patients for that arm.
Pre-assignment details
8 of the 151 enrolled patients were not randomized to treatment groups for the following reasons - 8 patients were incorrectly enrolled (ie did not comply with one or more inclusion / exclusion criteria).
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant 250 mg Fulvestrant 250 mg | 45 |
| Fulvestrant 250 mg + Loading Dose Fulvestrant 250 mg + Loading Dose | 51 |
| Fulvestrant 500 mg Fulvestrant 500 mg | 47 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Disease Progression | 27 | 31 | 28 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Subjective Disease Progression | 1 | 2 | 2 |
| Overall Study | Tumor Marker Elevation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Fulvestrant 250 mg | Fulvestrant 250 mg + Loading Dose | Fulvestrant 500 mg | Total |
|---|---|---|---|---|
| Age Continuous | 62.5 Years STANDARD_DEVIATION 7.4 | 62.4 Years STANDARD_DEVIATION 9.5 | 62.7 Years STANDARD_DEVIATION 9.1 | 62.5 Years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 45 Participants | 51 Participants | 47 Participants | 143 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 | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 45 | 49 / 51 | 44 / 46 |
| serious Total, serious adverse events | 2 / 45 | 5 / 51 | 1 / 46 |
Outcome results
Primary
Objective Response Rate (ORR)
An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response. Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization
Time frame: baseline and every 12 weeks (+/- 2weeks) from randomization data up to data cut-off (19th march 2008)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | Objective Response Rate (ORR) | 11.1 percentage of participants |
| Fulvestrant 250 mg + Loading Dose | Objective Response Rate (ORR) | 17.6 percentage of participants |
| Fulvestrant 500 mg | Objective Response Rate (ORR) | 10.6 percentage of participants |
Secondary
Clinical Benefit Rate (CBR)
A Clinical Benefit (CB) responder is defined as a patient having a best overall response of Complete response (CR), Partial Response (PR) or Stable disease (SD) provided SD (or better) was present = 154 days from randomization (ie SD = 24 weeks with the 2 week RECIST assessment time window allowed). The Clinical Benefit Rate is the percentage of patients with CB.
Time frame: every 12 weeks(+/- 2 weeks) from randomization to data up to data cut-off, 19th March 2008.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | Clinical Benefit Rate (CBR) | 42.2 percentage of participants |
| Fulvestrant 250 mg + Loading Dose | Clinical Benefit Rate (CBR) | 54.9 percentage of participants |
| Fulvestrant 500 mg | Clinical Benefit Rate (CBR) | 46.8 percentage of participants |
Secondary
Duration of Response (DoR)
Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieved a confirmed Complete Response or confirmed Partial Response.
Time frame: RECIST tumour assessments carried out every 12 weeks from randomisation (+/- 2 weeks) until data cut-off on19th March 2008.
Secondary
Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body
The measure of dispersion for mean population clearance is based on the estimated inter-individual variance
Time frame: Baseline to 12 weeks
Population: Patients who agreed to participate in the PK substudy. The results are based on 148, 122 and 140 plasma-concentration records from patients in the 250 mg, 250 mg + LD and 500 mg treatment arms respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant 250 mg | Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body | 34.4 L/h | Standard Deviation 0.096 |
Secondary
Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes
The measure of dispersion for volume of distribution is based on the inter-individual variance estimated for the apparent volume of plasma into which Fulvestrant distributes
Time frame: Baseline to 12 weeks
Population: Patients who agreed to participate in the PK substudy.
| Arm | Measure | Value (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 | 35300 Vss/F (L) | Standard Deviation 0.175 |
Secondary
Time to Progression (TTP)
Time (in days) from randomization until objective disease progression or death (in the absence of objective progression). RECIST tumour assessments carried out every 12 weeks from randomization (+/- 2 weeks) until data cut-off on 19th March 2008.
Time frame: every 12 weeks from randomization (+/- 2 weeks) until data cut-off (19th march 2008)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 250 mg | Time to Progression (TTP) | 169 days |
| Fulvestrant 250 mg + Loading Dose | Time to Progression (TTP) | 211 days |
| Fulvestrant 500 mg | Time to Progression (TTP) | 169 days |