Advanced Breast Cancer
Conditions
Keywords
oncology, cancer, breast cancer
Brief summary
The primary objective is to evaluate whether Zoladex 10.8 mg (12-weekly) is non-inferior to Zoladex 3.6 mg (4-weekly) in pre-menopausal women with oestrogen receptor positive advanced breast cancer by assessment of progression-free survival at 24 weeks. Secondary Objectives are to compare the safety and tolerability profile of ZOLADEX 10.8 mg and ZOLADEX 3.6 mg by assessment of adverse events (AEs)and to assess goserelin PK in Japanese and Caucasian participants who have received ZOLADEX 10.8 mg by assessment of goserelin plasma concentration time profiles Recruitment into the study has been permanently stopped as of 24 December 2007 due to slow recruitment. 98 (vs the planned 260) patients were randomised into the study and will be followed as per protocol for 2 years
Interventions
DRUGGoserelin acetate
3.6 mg intramuscular depot injection given every 4 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pre-menopausal women aged 18 years or over with histologically/cytologically-confirmed oestrogen receptor positive (ER +ve) breast cancer * World Health Organization (WHO) performance status of 0, 1, or 2 * Provided written informed consent
Exclusion criteria
* Treatment with tamoxifen or other hormonal therapies as early breast cancer (EBC) adjuvant in the previous 24 weeks * Received radiotherapy within the past 4 weeks * History of systemic malignancy other than breast cancer within the previous 3 years * Estimated survival less than 24 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression Free Survival (PFS) at Week 24 | Objective tumour assessments carried out every 12 weeks (+/- 7 days) until Week 24, and then every 24 weeks (+/- 14 days) until Week 96 or objective progression is confirmed according to Response Evaluation Criteria in Solid Tumours (RECIST). | The number of participants for whom neither objective disease progression or death (due to any cause) has been observed at Week 24 over the number of randomised participants x 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) at Week 24 | Response Evaluation Criteria in Solid Tumours (RECIST) tumour assessments carried out every 12 weeks from randomisation until Week 24 in those patients with measurable disease at baseline. | Number of participants who were objective responders at Week 24 over the number of participants evaluable for response x 100. An objective responder = a participants whose best unconfirmed response is either CR (Complete Response Disappearance of all target lesions) or PR (Partial Response At least a 30% decrease in target lesions) |
| Oestradiol (E2) Serum Concentrations at Week 24 | Blood samples for measurement of E2 concentrations collected from all patients at scheduled visits of screening, Day 1 and Weeks 12 and 24 (+/- 7 days). Week 24 data is presented | A comparison of mean E2 serum concentrations at timepoint(s) post Day 1 performed using analysis of covariance (ANCOVA), with treatment group, baseline E2 serum concentrations and country as covariates. Data analysed on the log scale; log scale mean and pooled log scale standard deviation from Analysis of Covariance (ANCOVA) presented. |
| Maximum Plasma Concentration, Cmax (ng/mL) | Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup | Maximum plasma concentration, Cmax (ng/mL), derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg) |
| Time to Maximum Plasma Concentration, Tmax (Hours) | Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup | Time to maximum plasma concentration, Tmax (hours), derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg) |
| Area Under the Plasma Concentration Curve (0-12 Weeks) | Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup | Area under the plasma concentration curve (0-12 weeks) derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg) |
Countries
Czechia, Russia, Ukraine
Participant flow
Recruitment details
Pre-menopausal women with Oestrogen Receptor Positive Advanced Breast Cancer were recruited between 25th April 2006 and 24th December 2007. 49 participants were randomised to ZOLADEX 10.8 mg and 49 participants were randomised to ZOLADEX 3.6 mg. One participant was randomised to ZOLADEX 3.6 mg but received ZOLADEX 10.8 mg.
Pre-assignment details
53 of the151 screened participants were not randomised to treatment groups for the following reasons : 50 participants were incorrectly enrolled (i.e. did not comply with inclusions/exclusion criteria) and a bone scan was not performed for 3 participants.
Participants by arm
| Arm | Count |
|---|---|
| ZOLADEX 10.8 mg ZOLADEX (goserelin acetate) 10.8 mg intramuscular depot for injection every 12 weeks | 49 |
| ZOLADEX 3.6 mg ZOLADEX (goserelin acetate) 3.6 mg intramuscular depot for injection every 4 weeks | 49 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Disease Progression | 30 | 25 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Reasons not specified | 5 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 4 |
Baseline characteristics
| Characteristic | ZOLADEX 10.8 mg | ZOLADEX 3.6 mg | Total |
|---|---|---|---|
| Age Continuous | 42.0 Years STANDARD_DEVIATION 6.45 | 42.6 Years STANDARD_DEVIATION 6.07 | 42.3 Years STANDARD_DEVIATION 6.24 |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 27 Participants | 32 Participants | 59 Participants |
| Race/Ethnicity, Customized Oriental | 22 Participants | 17 Participants | 39 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 49 Participants | 49 Participants | 98 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 | 39 / 50 | 37 / 48 |
| serious Total, serious adverse events | 2 / 50 | 3 / 48 |
Outcome results
Primary
Percentage of Participants With Progression Free Survival (PFS) at Week 24
The number of participants for whom neither objective disease progression or death (due to any cause) has been observed at Week 24 over the number of randomised participants x 100.
Time frame: Objective tumour assessments carried out every 12 weeks (+/- 7 days) until Week 24, and then every 24 weeks (+/- 14 days) until Week 96 or objective progression is confirmed according to Response Evaluation Criteria in Solid Tumours (RECIST).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZOLADEX 10.8 mg | Percentage of Participants With Progression Free Survival (PFS) at Week 24 | 69.4 Percentage of participants |
| ZOLADEX 3.6 mg | Percentage of Participants With Progression Free Survival (PFS) at Week 24 | 73.5 Percentage of participants |
Secondary
Area Under the Plasma Concentration Curve (0-12 Weeks)
Area under the plasma concentration curve (0-12 weeks) derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg)
Time frame: Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup
Population: participants in the PK subgroup set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ZOLADEX 10.8 mg | Area Under the Plasma Concentration Curve (0-12 Weeks) | 33.021 ng/mL |
Secondary
Maximum Plasma Concentration, Cmax (ng/mL)
Maximum plasma concentration, Cmax (ng/mL), derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg)
Time frame: Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup
Population: participants in the pharmacokinetic (PK) subgroup
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ZOLADEX 10.8 mg | Maximum Plasma Concentration, Cmax (ng/mL) | 4.565 ng/mL |
Secondary
Objective Response Rate (ORR) at Week 24
Number of participants who were objective responders at Week 24 over the number of participants evaluable for response x 100. An objective responder = a participants whose best unconfirmed response is either CR (Complete Response Disappearance of all target lesions) or PR (Partial Response At least a 30% decrease in target lesions)
Time frame: Response Evaluation Criteria in Solid Tumours (RECIST) tumour assessments carried out every 12 weeks from randomisation until Week 24 in those patients with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZOLADEX 10.8 mg | Objective Response Rate (ORR) at Week 24 | 28.9 Percentage of participants |
| ZOLADEX 3.6 mg | Objective Response Rate (ORR) at Week 24 | 25.6 Percentage of participants |
Secondary
Oestradiol (E2) Serum Concentrations at Week 24
A comparison of mean E2 serum concentrations at timepoint(s) post Day 1 performed using analysis of covariance (ANCOVA), with treatment group, baseline E2 serum concentrations and country as covariates. Data analysed on the log scale; log scale mean and pooled log scale standard deviation from Analysis of Covariance (ANCOVA) presented.
Time frame: Blood samples for measurement of E2 concentrations collected from all patients at scheduled visits of screening, Day 1 and Weeks 12 and 24 (+/- 7 days). Week 24 data is presented
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| ZOLADEX 10.8 mg | Oestradiol (E2) Serum Concentrations at Week 24 | 1.42 pmol/L | Standard Deviation 0.99 |
| ZOLADEX 3.6 mg | Oestradiol (E2) Serum Concentrations at Week 24 | 1.49 pmol/L | Standard Deviation 0.99 |
Secondary
Time to Maximum Plasma Concentration, Tmax (Hours)
Time to maximum plasma concentration, Tmax (hours), derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg)
Time frame: Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup
Population: participants in the PK subgroup set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ZOLADEX 10.8 mg | Time to Maximum Plasma Concentration, Tmax (Hours) | 1.9 hours |