Breast Neoplasms
Conditions
Keywords
metastatic breast cancer
Brief summary
The primary purpose of the study is to determine the time to progression of the combination of study drug (AG-013736) and docetaxel versus docetaxel alone in patients who have not received prior chemotherapy for metastatic breast cancer. The secondary purpose of the study is to determine the dose of study drug that can be given with docetaxel administered on an every 3 week schedule.
Interventions
DRUGPlacebo
5 mg twice daily \[bid\] continuous dosing
DRUGDocetaxel
Standard of care drug administration
5mg twice daily \[bid\] continuous dosing
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patients with histologically/cytologically proven metastatic breast carcinoma (stage IV, or recurrent with local or regional spread or distant metastatic disease) * Adequate bone marrow, liver, and renal function
Exclusion criteria
* Adjuvant chemotherapy given in the past 12 months * Uncontrolled brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tumor Progression (TTP) | Phase 2 double-blind baseline until tumor progression or death or discontinuation from study treatment, assessed every 9 weeks up to 129 weeks | Time in days from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind) | Phase 2 double- blind baseline until the date of first documented progression or discontinuation from the study treatment due to any cause, assessed every 9 weeks up to 129 weeks | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
| Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label) | Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
| Duration of Response (DR) for Phase 2 (Double-blind) | Phase 2 double-blind baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 9 weeks up to 129 weeks | Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Duration of Response (DR) for Phase 2 (Open-label) | Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks | Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Population Pharmacokinetics of Axitinib (AG-013736) for Phase 2 (Double-blind) | Day 1 (pre-dose), Day 22 and Day 43 and then every 9 weeks up to 129 weeks | Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules. |
Countries
Canada, Czechia, Germany, India, Italy, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Participants who progressed in Docetaxel + Placebo (Phase 2, Double-blind) after consent were eligible to continue to open-label phase. 16 participants crossed-over to open-label phase.
Participants by arm
| Arm | Count |
|---|---|
| Axitinib + Docetaxel (Phase 1, Lead-in) Axitinib (AG-013736) 5 mg tablet orally twice daily BID starting from Day 3 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m\^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. | 6 |
| Axitinib + Docetaxel (Phase 2, Double-blind) Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m\^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. | 112 |
| Docetaxel + Placebo (Double-blind) Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m\^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued with axitinib (AG-013736) 5 mg tablet orally BID continuously in cycles of 4 weeks. | 56 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase 1, Lead-in | Adverse Event | 1 | 0 | 0 | 0 |
| Phase 1, Lead-in | Clinical progression | 1 | 0 | 0 | 0 |
| Phase 1, Lead-in | Lack of Efficacy | 4 | 0 | 0 | 0 |
| Phase 2, Double-blind | Adverse Event | 0 | 25 | 6 | 0 |
| Phase 2, Double-blind | Lack of Efficacy | 0 | 59 | 40 | 0 |
| Phase 2, Double-blind | Randomized but not treated | 0 | 1 | 0 | 0 |
| Phase 2, Double-blind | Un-specified | 0 | 14 | 6 | 0 |
| Phase 2, Double-blind | Withdrawal by Subject | 0 | 13 | 4 | 0 |
| Phase 2, Open-label | Adverse Event | 0 | 0 | 0 | 2 |
| Phase 2, Open-label | Lack of Efficacy | 0 | 0 | 0 | 11 |
| Phase 2, Open-label | Other | 0 | 0 | 0 | 2 |
| Phase 2, Open-label | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Axitinib + Docetaxel (Phase 1, Lead-in) | Axitinib + Docetaxel (Phase 2, Double-blind) | Docetaxel + Placebo (Double-blind) | Total |
|---|---|---|---|---|
| Age Continuous | 50.80 Years STANDARD_DEVIATION 9.68 | 54.10 Years STANDARD_DEVIATION 10.43 | 54.70 Years STANDARD_DEVIATION 10.12 | 54.2 Years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 6 Participants | 112 Participants | 56 Participants | 174 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 | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 111 / 111 | 56 / 56 | 12 / 16 |
| serious Total, serious adverse events | 1 / 6 | 54 / 111 | 17 / 56 | 2 / 16 |
Outcome results
Primary
Time to Tumor Progression (TTP)
Time in days from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]).
Time frame: Phase 2 double-blind baseline until tumor progression or death or discontinuation from study treatment, assessed every 9 weeks up to 129 weeks
Population: Study population included all randomized participants who had a baseline assessment of disease and the correct histological cancer type.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | Time to Tumor Progression (TTP) | 247 days |
| Docetaxel + Placebo (Phase 2, Double-blind) | Time to Tumor Progression (TTP) | 215 days |
Comparison: P-value was calculated using one-sided Log rank test, stratified for estrogen receptor (ER) status (ER-positive or ER-negative/unknown), prior adjuvant chemotherapy (yes or no), and Eastern Cooperative Oncology Group (ECOG) performance status (less than or equal to \[=\<1\] or 2). The stratified Cox proportional hazards model was fitted, using the same stratification variables as above.p-value: 0.15695% CI: [0.819, 1.867]Log Rank
Secondary
Duration of Response (DR) for Phase 2 (Double-blind)
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time frame: Phase 2 double-blind baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 9 weeks up to 129 weeks
Population: Subgroup of participants from the study population with a confirmed objective tumor response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | Duration of Response (DR) for Phase 2 (Double-blind) | 211 days |
| Docetaxel + Placebo (Phase 2, Double-blind) | Duration of Response (DR) for Phase 2 (Double-blind) | 149 days |
Secondary
Duration of Response (DR) for Phase 2 (Open-label)
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time frame: Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks
Population: Subgroup of participants from the AT population with a confirmed objective tumor response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | Duration of Response (DR) for Phase 2 (Open-label) | 1.0 days |
Secondary
Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind)
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: Phase 2 double- blind baseline until the date of first documented progression or discontinuation from the study treatment due to any cause, assessed every 9 weeks up to 129 weeks
Population: Study population included all randomized participants who had a baseline assessment of disease and the correct histological cancer type.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind) | 41.1 percentage of participants |
| Docetaxel + Placebo (Phase 2, Double-blind) | Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind) | 23.6 percentage of participants |
p-value: 0.03895% CI: [3, 31.9]Fisher Exact
Secondary
Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label)
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks
Population: All treated (AT) population included participants from Phase 2 who progressed by RECIST criteria while in the placebo + docetaxel treatment group and had a baseline disease assessment and received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label) | 6.3 percentage of participants |
Other Pre-specified
Population Pharmacokinetics of Axitinib (AG-013736) for Phase 2 (Double-blind)
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time frame: Day 1 (pre-dose), Day 22 and Day 43 and then every 9 weeks up to 129 weeks