Breast Neoplasms
Conditions
Brief summary
This is an open-label, multicenter, randomized (1:1 randomization ratio) study of either exemestane or exemestane plus celecoxib in postmenopausal women with ABC having progressed on tamoxifen.
Interventions
DRUGExemestane
Patient will be instructed to take a 25 mg exemestane tablet, once a day, every day, with food.
DRUGCelecoxib + Exemestane
Exemestane + celecoxib treatment arm, she will be instructed to take also two x 200 mg celecoxib capsules twice a day, every day, with food.
Sponsors
Pfizer
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
* Postmenopausal female patient with histologically or cytologically confirmed breast cancer having progressed on Tamoxifen. * Advanced disease: patients with advanced breast carcinoma with disease progression who had progressed/relapsed following \> 8 weeks of treatment with Tamoxifen for advanced disease; or progressed during adjuvant Tamoxifen for at least 6 or 12 months depending on receptor status; or progressed within 12 months from completion of adjuvant treatment with Tamoxifen. * at least one measurable lesion
Exclusion criteria
* More than one previous chemotherapy and/or more than one hormonotherapy for advanced disease. * Previous hormonotherapy for advanced disease other than Tamoxifen. * Myocardial infarction within previous 6 mo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Clinical Benefit | Baseline, Week 8, 16, 24, and every 12 weeks beyond 24 up to Week 108 and every 24 weeks thereafter until 9 months following last subject last visit (LSLV) | Clinical benefit was based on objective tumor assessments made according to Response Evaluation Criteria (RECIST) system of unidimensional evaluation. Includes subjects with complete response (CR), partial response (PR), and long term disease stabilization (SD) for at least 24 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Clinical Benefit | Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV | Time from randomization date to first objective documentation of tumor progression or death due to tumor progression in the absence of previous documentation of tumor progression. |
| Duration of Objective Response (in Subjects With CR or PR) | Baseline, Weeks 8, 16, 24, every 12 weeks beyond 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV | Time from the first objective documentation of response until the first objective documentation of tumor progression. |
| Duration of Long-Term SD | Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months LSLV | Time from start of treatment until the first objective documentation of tumor progression or death due to tumor progression in the absence of previous documentation of tumor progression in subjects with long-term SD. |
| Number of Subjects With Objective Response | Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV | Objective tumor response includes subjects with CR or PR according to RECIST. |
| Time to Treatment Failure | Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV | Time from randomization to first objective tumor recurrence or progression or death due to any cause or withdrawal from study treatment due to any reason, whichever was the earliest. |
| Survival | Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV or death | Time from randomization to date of death (any cause). |
| Time to Tumor Progression | Baseline, Weeks 8, 16, 24, every 12 weeks beyond Week 24 up to Week 108 and every 24 weeks thereafter until 9 months following LSLV | Time from randomization to first objective tumor recurrence or progression or death due to tumor progression in the absence of previous documentation of tumor progression. |
Countries
Belgium, Brazil, Canada, Colombia, India, Mexico, Peru, Philippines, United States
Participant flow
Pre-assignment details
2 subjects in the exemestane arm were never treated. One subject refused to be treated having originally consented to participate in this study and the other, reason for not starting treatment was unknown
Participants by arm
| Arm | Count |
|---|---|
| Exemestane (Exemestane Alone) oral dose exemestane taken with food (25 mg tablet once daily) | 55 |
| Combination (Exemestane + Celecoxib) oral doses to be taken with food (25 mg tablet exemestane once daily; celecoxib 2 x 200 mg tablets twice daily) | 56 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Lack of Efficacy | 48 | 41 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Randomized/never treated | 2 | 0 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Exemestane (Exemestane Alone) | Combination (Exemestane + Celecoxib) | Total |
|---|---|---|---|
| Age, Customized 50-64 years | 20.0 Participants | 27.0 Participants | 47.0 Participants |
| Age, Customized < 50 years | 20.0 Participants | 16.0 Participants | 36.0 Participants |
| Age, Customized 65-79 years | 15.0 Participants | 12.0 Participants | 27.0 Participants |
| Age, Customized => 80 years | 0.0 Participants | 1.0 Participants | 1.0 Participants |
| Sex: Female, Male Female | 55 Participants | 56 Participants | 111.0 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / — | 43 / — |
| serious Total, serious adverse events | 9 / — | 14 / — |
Outcome results
Primary
Number of Subjects With Clinical Benefit
Clinical benefit was based on objective tumor assessments made according to Response Evaluation Criteria (RECIST) system of unidimensional evaluation. Includes subjects with complete response (CR), partial response (PR), and long term disease stabilization (SD) for at least 24 weeks.
Time frame: Baseline, Week 8, 16, 24, and every 12 weeks beyond 24 up to Week 108 and every 24 weeks thereafter until 9 months following last subject last visit (LSLV)
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane (Exemestane Alone) | Number of Subjects With Clinical Benefit | 24 participants |
| Combination (Exemestane + Celecoxib) | Number of Subjects With Clinical Benefit | 24 participants |
95% CI: [34.4, 63.7]
95% CI: [32.9, 61.5]
Secondary
Duration of Clinical Benefit
Time from randomization date to first objective documentation of tumor progression or death due to tumor progression in the absence of previous documentation of tumor progression.
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV
Population: Evaluable population. Number of participants analyzed = number of subjects with clinical benefit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane (Exemestane Alone) | Duration of Clinical Benefit | 49.1 weeks |
| Combination (Exemestane + Celecoxib) | Duration of Clinical Benefit | 96.6 weeks |
Secondary
Duration of Long-Term SD
Time from start of treatment until the first objective documentation of tumor progression or death due to tumor progression in the absence of previous documentation of tumor progression in subjects with long-term SD.
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months LSLV
Population: Evaluable population. Number of participants analyzed = number of subjects with long-term SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane (Exemestane Alone) | Duration of Long-Term SD | 52.9 weeks |
| Combination (Exemestane + Celecoxib) | Duration of Long-Term SD | 109.7 weeks |
Secondary
Duration of Objective Response (in Subjects With CR or PR)
Time from the first objective documentation of response until the first objective documentation of tumor progression.
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks beyond 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV
Population: Evaluable population. Number of participants analyzed = number of subjects with objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane (Exemestane Alone) | Duration of Objective Response (in Subjects With CR or PR) | 32.7 weeks |
| Combination (Exemestane + Celecoxib) | Duration of Objective Response (in Subjects With CR or PR) | 40.1 weeks |
Secondary
Number of Subjects With Objective Response
Objective tumor response includes subjects with CR or PR according to RECIST.
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane (Exemestane Alone) | Number of Subjects With Objective Response | 11 participants |
| Combination (Exemestane + Celecoxib) | Number of Subjects With Objective Response | 12 participants |
95% CI: [11.8, 36.6]
95% CI: [12.8, 37.5]
Secondary
Survival
Time from randomization to date of death (any cause).
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV or death
Population: Evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane (Exemestane Alone) | Survival | 74.4 weeks |
| Combination (Exemestane + Celecoxib) | Survival | 73.9 weeks |
Secondary
Time to Treatment Failure
Time from randomization to first objective tumor recurrence or progression or death due to any cause or withdrawal from study treatment due to any reason, whichever was the earliest.
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks from Week 24 up to Week 108, and every 24 weeks thereafter until 9 months following LSLV
Population: Evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane (Exemestane Alone) | Time to Treatment Failure | 18.1 Weeks |
| Combination (Exemestane + Celecoxib) | Time to Treatment Failure | 20.4 Weeks |
Secondary
Time to Tumor Progression
Time from randomization to first objective tumor recurrence or progression or death due to tumor progression in the absence of previous documentation of tumor progression.
Time frame: Baseline, Weeks 8, 16, 24, every 12 weeks beyond Week 24 up to Week 108 and every 24 weeks thereafter until 9 months following LSLV
Population: Evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane (Exemestane Alone) | Time to Tumor Progression | 20 weeks |
| Combination (Exemestane + Celecoxib) | Time to Tumor Progression | 23.4 weeks |