Breast Neoplasms
Conditions
Brief summary
The treatment received with sunitinib plus capecitabine could delay tumor growth longer than with treatment with capecitabine alone.
Interventions
DRUGSunitinib + Capecitabine
Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m\^2 per day \[1000 mg/m\^2 bid (twice daily)\] from days 1-14 every 3 weeks. Study treatment should be given until progression or withdrawal from the study for other reasons.
DRUGCapecitabine
Capecitabine administered orally at a starting dose of 2500 mg/m\^2 per day \[1250 mg/m\^2 bid (twice daily)\] from days 1-14 every 3 weeks. Study treatment should be given until progression or withdrawal from the study for other reasons. At the time of progression, patients may be eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally advanced or metastatic disease that can be measured. Patients with bone-only disease are also allowed to enter the study. * Previous treatment with an anthracycline and a taxane in any setting * Progression on first or second line regimen or adjuvant regimen if disease free interval less than 12 months
Exclusion criteria
* History of inflammatory carcinoma if there is no other measurable disease * More than 2 chemotherapy agents in the advanced disease setting * Brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline until disease progression (up to 3 years from first dose) | Defined as the time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date minus randomization date plus 1) divided by 30.4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DR) | Baseline until response or disease progression (up to 3 years from first dose) | Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR (in months) was calculated as \[the date response ended (date of PD or death) minus first CR or PR date that was subsequently confirmed plus 1)\] divided by 30.4. |
| Overall Survival (OS) | Baseline until death or up to 3 years from first dose | Time from the date of randomization to the date of death due to any cause. OS (in months) calculated as (date of death minus randomization date plus 1) divided by 30.4. For patients lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Patients lacking survival data beyond randomization had their OS times censored at randomization. |
| Percent Chance of Participant Survival | Year 1, Year 2, Year 3 | Probability of survival 2 years and 3 years after the first dose of study treatment. |
| Percentage of Participants With Objective Response (OR) | Baseline until response or disease progression (up to 3 years from first dose) | Proportion of participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST); CR: disappearance of all target lesions, PR: greater than or equal to (\>=) 30 percent (%) decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD. Confirmed responses = persist on repeat imaging study at least 4 weeks after initial documentation of response. Designation of best response of stable disease (SD) required the criteria to be met at least 5 weeks after randomization. |
| Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23) | Day 1 of each treatment cycle (up to 3 years or end of treatment) | BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. |
| Change From Baseline in EuroQol Group's EuroQol 5-Dimensional Self-Report Questionnaire (EQ-5D) | Day 1 of each treatment cycle (up to 3 years or end of treatment) | EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant. |
| Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire (EORTC QLQ-C30) | Day 1 of each treatment cycle (up to 3 years or end of treatment) | EORTC QLQ-C30: global health/quality of life (QoL), functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms |
Countries
Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Ireland, Italy, Netherlands, Norway, Poland, Romania, Russia, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib + Capecitabine Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m\^2 per day (1000 mg/m\^2 BID) from Days 1-14 every 3 weeks. | 221 |
| Capecitabine Capecitabine administered orally at a starting dose of 2500 mg/m\^2 per day (1250 mg/m\^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously. | 221 |
| Total | 442 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 8 |
| Overall Study | Death | 8 | 6 | 6 |
| Overall Study | Global deterioration of health status | 0 | 0 | 4 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 |
| Overall Study | Objective progression or relapse | 158 | 93 | 58 |
| Overall Study | Other | 45 | 30 | 1 |
| Overall Study | Protocol Violation | 1 | 2 | 0 |
| Overall Study | Sponsor decision | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 7 | 1 |
Baseline characteristics
| Characteristic | Sunitinib + Capecitabine | Capecitabine | Total |
|---|---|---|---|
| Age, Customized Greater than or equal to 65 years | 39 participants | 36 participants | 75 participants |
| Age, Customized Less than 65 years | 182 participants | 185 participants | 367 participants |
| Sex: Female, Male Female | 218 Participants | 220 Participants | 438 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 214 / 217 | 208 / 215 |
| serious Total, serious adverse events | 85 / 217 | 59 / 215 |
Outcome results
Primary
Progression Free Survival (PFS)
Defined as the time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date minus randomization date plus 1) divided by 30.4.
Time frame: Baseline until disease progression (up to 3 years from first dose)
Population: Intent to treat (ITT) population: defined as all participants who were randomized
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib + Capecitabine | Progression Free Survival (PFS) | Independent radiology assessment | 5.5 months |
| Sunitinib + Capecitabine | Progression Free Survival (PFS) | Investigator's assessment | 5.4 months |
| Capecitabine | Progression Free Survival (PFS) | Independent radiology assessment | 5.9 months |
| Capecitabine | Progression Free Survival (PFS) | Investigator's assessment | 5.5 months |
Comparison: A stratified log-rank test (1-sided, α=0.025) based on randomization stratification factorsp-value: 0.940995% CI: [0.9487, 1.5789]Log Rank
Comparison: A stratified log-rank test (1-sided, α=0.025) based on randomization stratification factorsp-value: 0.81295% CI: [0.8817, 1.3935]Log Rank
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23)
BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Time frame: Day 1 of each treatment cycle (up to 3 years or end of treatment)
Population: PRO assessments were not analyzed because the study did not meet its primary endpoint.
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire (EORTC QLQ-C30)
EORTC QLQ-C30: global health/quality of life (QoL), functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms
Time frame: Day 1 of each treatment cycle (up to 3 years or end of treatment)
Population: Patient Reported Outcomes (PRO) assessments were not analyzed because the study did not meet its primary endpoint.
Secondary
Change From Baseline in EuroQol Group's EuroQol 5-Dimensional Self-Report Questionnaire (EQ-5D)
EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.
Time frame: Day 1 of each treatment cycle (up to 3 years or end of treatment)
Population: PRO assessments were not analyzed because the study did not meet its primary endpoint.
Secondary
Duration of Response (DR)
Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR (in months) was calculated as \[the date response ended (date of PD or death) minus first CR or PR date that was subsequently confirmed plus 1)\] divided by 30.4.
Time frame: Baseline until response or disease progression (up to 3 years from first dose)
Population: ITT subgroup of participants with a confirmed objective tumor response.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib + Capecitabine | Duration of Response (DR) | Investigator's assessment | 5.7 months |
| Sunitinib + Capecitabine | Duration of Response (DR) | Independent radiology assessment | 9.0 months |
| Capecitabine | Duration of Response (DR) | Independent radiology assessment | 8.8 months |
| Capecitabine | Duration of Response (DR) | Investigator's assessment | 7.6 months |
Secondary
Overall Survival (OS)
Time from the date of randomization to the date of death due to any cause. OS (in months) calculated as (date of death minus randomization date plus 1) divided by 30.4. For patients lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Patients lacking survival data beyond randomization had their OS times censored at randomization.
Time frame: Baseline until death or up to 3 years from first dose
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib + Capecitabine | Overall Survival (OS) | 16.5 months |
| Capecitabine | Overall Survival (OS) | 17.2 months |
p-value: 0.627595% CI: [0.8322, 1.2927]Log Rank
Secondary
Percentage of Participants With Objective Response (OR)
Proportion of participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST); CR: disappearance of all target lesions, PR: greater than or equal to (\>=) 30 percent (%) decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD. Confirmed responses = persist on repeat imaging study at least 4 weeks after initial documentation of response. Designation of best response of stable disease (SD) required the criteria to be met at least 5 weeks after randomization.
Time frame: Baseline until response or disease progression (up to 3 years from first dose)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Capecitabine | Percentage of Participants With Objective Response (OR) | Independent radiology assessment | 18.6 percentage of participants |
| Sunitinib + Capecitabine | Percentage of Participants With Objective Response (OR) | Investigator's assessment | 25.3 percentage of participants |
| Capecitabine | Percentage of Participants With Objective Response (OR) | Independent radiology assessment | 16.3 percentage of participants |
| Capecitabine | Percentage of Participants With Objective Response (OR) | Investigator's assessment | 20.4 percentage of participants |
Comparison: Independent radiology assessmentp-value: 0.314395% CI: [0.69, 1.97]Cochran-Mantel-Haenszel
Comparison: Investigator's assessmentp-value: 0.126995% CI: [0.83, 2.13]Cochran-Mantel-Haenszel
Secondary
Percent Chance of Participant Survival
Probability of survival 2 years and 3 years after the first dose of study treatment.
Time frame: Year 1, Year 2, Year 3
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Capecitabine | Percent Chance of Participant Survival | Year 1 | 0.635 probability of survival |
| Sunitinib + Capecitabine | Percent Chance of Participant Survival | Year 2 | 0.368 probability of survival |
| Sunitinib + Capecitabine | Percent Chance of Participant Survival | Year 3 | 0.150 probability of survival |
| Capecitabine | Percent Chance of Participant Survival | Year 1 | 0.654 probability of survival |
| Capecitabine | Percent Chance of Participant Survival | Year 2 | 0.373 probability of survival |
| Capecitabine | Percent Chance of Participant Survival | Year 3 | 0.174 probability of survival |