Breast Cancer
Conditions
Keywords
ZOLADEX, Pre-menopausal, Oestrogen Receptor, Advanced Breast Cancer, Progression Free Survival
Brief summary
The purpose of this study is to examine the efficacy and safety as well as the characteristics of the female hormone and study medications after administration in pre-menopausal women with estrogen receptor positive advanced breast cancer who were randomised in a 1:1 ratio to either of the two treatment groups; the ZD9393 3.6 mg depot group or ZD9393 10.8 mg depot group, both given in combination with tamoxifen tablets.
Interventions
DRUGZD9393 (Zoladex) 10.8 mg
10.8 mg (goserelin acetate): one subcutaneous depot injection once every 12 weeks (± 7 days).
DRUGZD9393 (Zoladex) 3.6 mg
3.6 mg (goserelin acetate): one subcutaneous depot injection once every 4 weeks (± 7 days).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Female ≥20 years and pre-menopausal.Pre-menopausal defined as 1) last menses within 1 year of randomisation, and 2) E2 ≥10 pg/mL and FSH ≤ 30 mIU/mL within 4 weeks of randomisation. * Hormone sensitivity (ER positive) of primary or secondary tumour tissue. * Histological/cytological confirmation of breast cancer and are candidates to receive hormonal therapy as therapy for advanced breast cancer.
Exclusion criteria
* Patients who have received tamoxifen or other hormonal therapies as adjuvant therapy for breast cancer within 24 weeks before randomisation and/or who have received prior treatment with hormonal therapies for advanced breast cancer * Patients who have received LHRHa as adjuvant therapy for breast cancer within 48 weeks before randomisation * Patients who have relapsed during adjuvant hormonal therapy or within 48 weeks after completion of adjuvant hormonal therapy and/or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Progression-free Survival (PFS) at 24 Weeks | 24 weeks after the first dosing | A patient is judged as progression-free survive at Week 24 if their PFS time is at least 24 weeks with no progression event prior to Week 24 (ie, overall visit response is complete response (CR), partial response (PR) or stable disease (SD) at a tumour assessment at least 24 weeks after randomization). Overall visit response is assessed according to the RECIST version 1.1. %PFS is the proportion of patients with PFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders at 24 Weeks | 24 weeks after the first dosing | Responders are defined as those patients with a best objective tumour response of CR or PR during the first 24 weeks of therapy. Tumour response is assessed according to the RECIST version 1.1. ORR is defined as the proportion of patients who are responders. |
| Oestradiol (E2) Serum Concentrations at 24 Weeks | 24 weeks after the first dosing | E2 serum concentrations (pg/mL) at 24 weeks |
Countries
India, Japan, Philippines, South Korea, Taiwan, Thailand
Participant flow
Recruitment details
Totally 286 patients were screened to the study from 58 centres in the following 6 countries: India, Japan, Korea, Philippines, Thailand, Taiwan. The first patient entered the study on 26 February 2010 and the last visit of last patient was on 19 September 2012.
Pre-assignment details
286 patients were screened and 222 patients were randomized (109 in ZOLADEX 10.8 mg, 113 in ZOLADEX 3.6 mg)
Participants by arm
| Arm | Count |
|---|---|
| Zoladex 10.8 mg ZOLADEX 10.8 mg (goserelin acetate): one subcutaneous depot injection into interior abdominal wall once every 12 weeks | 109 |
| Zoladex 3.6 mg ZOLADEX 3.6 mg (goserelin acetate): one subcutaneous depot injection into interior abdominal wall once every 4 weeks | 113 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Reasons other than below | 19 | 31 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Zoladex 10.8 mg | Total | Zoladex 3.6 mg |
|---|---|---|---|
| Age, Continuous | 40.9 years STANDARD_DEVIATION 6.9 | 40.9 years STANDARD_DEVIATION 6.4 | 40.9 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 222 Participants | 113 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 109 Participants | 222 Participants | 113 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Asia India | 29 Participants | 56 Participants | 27 Participants |
| Region of Enrollment Asia Japan | 29 Participants | 59 Participants | 30 Participants |
| Region of Enrollment Asia Philippines | 21 Participants | 44 Participants | 23 Participants |
| Region of Enrollment Asia Republic of Korea | 13 Participants | 28 Participants | 15 Participants |
| Region of Enrollment Asia Taiwan | 7 Participants | 16 Participants | 9 Participants |
| Region of Enrollment Asia Thailand | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Female | 109 Participants | 222 Participants | 113 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 | 4 / 108 | 3 / 113 |
| other Total, other adverse events | 47 / 108 | 52 / 113 |
| serious Total, serious adverse events | 4 / 108 | 8 / 113 |
Outcome results
Primary
Number of Patients With Progression-free Survival (PFS) at 24 Weeks
A patient is judged as progression-free survive at Week 24 if their PFS time is at least 24 weeks with no progression event prior to Week 24 (ie, overall visit response is complete response (CR), partial response (PR) or stable disease (SD) at a tumour assessment at least 24 weeks after randomization). Overall visit response is assessed according to the RECIST version 1.1. %PFS is the proportion of patients with PFS.
Time frame: 24 weeks after the first dosing
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoladex 10.8 mg | Number of Patients With Progression-free Survival (PFS) at 24 Weeks | 67 Participants |
| Zoladex 3.6 mg | Number of Patients With Progression-free Survival (PFS) at 24 Weeks | 68 Participants |
Comparison: CI for the difference (10.8 mg-3.6 mg) in %PFS at 24 weeks calculated using the score method recommended by Newcombe et al95% CI: [-11.4, 13.9]
Secondary
Number of Responders at 24 Weeks
Responders are defined as those patients with a best objective tumour response of CR or PR during the first 24 weeks of therapy. Tumour response is assessed according to the RECIST version 1.1. ORR is defined as the proportion of patients who are responders.
Time frame: 24 weeks after the first dosing
Population: Full Analysis Set (patients without measurable disease at baseline were excluded from analysis)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoladex 10.8 mg | Number of Responders at 24 Weeks | 21 Participants |
| Zoladex 3.6 mg | Number of Responders at 24 Weeks | 25 Participants |
Comparison: CI for the difference (10.8 mg-3.6 mg) in ORR at 24 weeks calculated using the score method recommended by Newcombe et al95% CI: [-15.47, 9.67]
Secondary
Oestradiol (E2) Serum Concentrations at 24 Weeks
E2 serum concentrations (pg/mL) at 24 weeks
Time frame: 24 weeks after the first dosing
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoladex 10.8 mg | Oestradiol (E2) Serum Concentrations at 24 Weeks | 20.302 pg/mL | Standard Deviation 12.251 |
| Zoladex 3.6 mg | Oestradiol (E2) Serum Concentrations at 24 Weeks | 24.798 pg/mL | Standard Deviation 28.149 |