Breast Neoplasms
Conditions
Keywords
advanced breast cancer, metastatic breast cancer, treatment resistant, treatment failure
Brief summary
To compare efficacy and safety of Sunitinib and Capecitabine in subjects with advanced breast cancer who failed both a taxane and an anthracycline chemotherapy regimen or failed with a taxane and for whom further anthracycline therapy is not indicated
Detailed description
Patient enrollment in this trial was discontinued based on statistical assessment for futility. An independent Data Monitoring Committee found that even if the trial had been allowed to continue, treatment with single agent sunitinib would be unable to demonstrate a statistically significant improvement in the primary endpoint of progression-free survival compared with single agent capecitabine in the study population. Pfizer notified clinical trial investigators involved in the study and regulatory agencies of these findings on 25Mar2009. Patients receiving sunitinib will be allowed to receive capecitabine or enter an extension trial if they are receiving clinical benefit from continued sunitinib therapy. There were no safety concerns leading to the decision to terminate the study.
Interventions
DRUGCapecitabine
1250 mg/m\^2, twice daily, for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
DRUGSunitinib malate
37.5 mg daily, continuous dosing
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
* breast adenocarcinoma * prior treatment with an anthracycline and a taxane either concurrently or sequentially in the neoadjuvant, adjuvant and or/ advanced disease treatment settings. No more than 1 chemotherapy regimen in the advanced setting
Exclusion criteria
* Prior treatment with regimens of chemotherapy in the advanced/metastatic disease setting beyond those containing anthracyclines and taxanes or multiple anthracyclines/ taxanes treatments. * Any prior regimen with capecitabine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From time of randomization to every 6 weeks thereafter through 22 months or until death | Time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occured first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response (OR) | From time of randomization to every 6 weeks thereafter through 22 months | OR was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.0) for at least 4 weeks, confirmed by repeat tumor assessments. CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to (\>=) 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) | From time of randomization to every 6 weeks thereafter through 22 months or death | Time from the first documentation of OR (CR or PR) that was subsequently confirmed to the first documentation of tumor progression or death due to any cause. CR was defined as disappearance of all target lesions. PR was defined as a \>= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. |
| Time to Tumor Response (TTR) | From time of randomization to every 6 weeks thereafter through 22 months | Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target lesions. PR was defined as a \>= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. |
| Time to Tumor Progression (TTP) | From time of randomization to every 6 weeks thereafter through 22 months | Time from randomization to first documentation of objective tumor progression. |
| European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) | From Day 1 of Cycle 1, then odd numbered cycles thereafter | EORTC QLQ-C30 scales: functional (physical/role/cognitive/emotional/social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms. |
| EORTC QLQ Breast Cancer Module (BR23) | From Day 1 of Cycle 1, then odd numbered cycles thereafter | 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 implied a greater degree of symptoms. |
| Overall Survival (OS) | From time of randomization until death | Average time from randomization to first documentation of death due to any cause. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, Colombia, France, Germany, Hong Kong, India, Italy, Japan, Mexico, Peru, Philippines, Singapore, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib 37.5 mg daily, continuous dosing | 238 |
| Capecitabine 1250 milligrams per square meter (mg/m\^2) or 1000 mg/m\^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles | 244 |
| Total | 482 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 38 | 24 |
| Overall Study | Death | 1 | 7 |
| Overall Study | Global deterioration of health status | 10 | 7 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Objective progression or relapse | 150 | 169 |
| Overall Study | Other | 14 | 17 |
| Overall Study | Protocol Violation | 5 | 1 |
| Overall Study | Study terminated by sponsor | 9 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 15 |
Baseline characteristics
| Characteristic | Sunitinib | Capecitabine | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 50 Participants | 70 Participants | 120 Participants |
| Age, Customized 45 to 64 years | 159 Participants | 129 Participants | 288 Participants |
| Age, Customized > = 65 years | 29 Participants | 45 Participants | 74 Participants |
| Sex/Gender, Customized Female | 238 Participants | 244 Participants | 482 Participants |
| Sex/Gender, Customized 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 | 228 / 238 | 229 / 240 |
| serious Total, serious adverse events | 72 / 238 | 44 / 240 |
Outcome results
Primary
Progression-Free Survival (PFS)
Time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occured first.
Time frame: From time of randomization to every 6 weeks thereafter through 22 months or until death
Population: Intent-to-treat (ITT) population: included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Progression-Free Survival (PFS) | 2.8 Months |
| Capecitabine | Progression-Free Survival (PFS) | 4.2 Months |
Comparison: Null hypothesis is that PFS (median=4.2 months) for sunitinib arm equals PFS for capecitabine arm. The study was designed to have 90% power to detect statistical difference in PFS between two treatment groups assuming the hazard ratio (sunitinib/capecitabine) is 0.75 and both arms follow exponential distribution.p-value: 0.00295% CI: [1.156, 1.869]Log Rank
Secondary
Duration of Response (DR)
Time from the first documentation of OR (CR or PR) that was subsequently confirmed to the first documentation of tumor progression or death due to any cause. CR was defined as disappearance of all target lesions. PR was defined as a \>= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.
Time frame: From time of randomization to every 6 weeks thereafter through 22 months or death
Population: ITT population. DR was calculated for the subgroup of participants with objective response. 27 participants in the sunitinib arm and 40 participants in the capecitabine arm reported CR or PR response and were analyzed for DR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Duration of Response (DR) | 6.9 Months |
| Capecitabine | Duration of Response (DR) | 9.3 Months |
p-value: 0.03795% CI: [1.042, 7.459]Log Rank
Secondary
EORTC QLQ Breast Cancer Module (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 implied a greater degree of symptoms.
Time frame: From Day 1 of Cycle 1, then odd numbered cycles thereafter
Population: The study was stopped early for futility and EORTC QLQ Cancer Module (BR23) analysis was not performed.
Secondary
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
EORTC QLQ-C30 scales: functional (physical/role/cognitive/emotional/social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms.
Time frame: From Day 1 of Cycle 1, then odd numbered cycles thereafter
Population: The study was stopped early for futility and EORTC QLQ-C30 analysis was not performed.
Secondary
Number of Participants With Overall Response (OR)
OR was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.0) for at least 4 weeks, confirmed by repeat tumor assessments. CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to (\>=) 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: From time of randomization to every 6 weeks thereafter through 22 months
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | Number of Participants With Overall Response (OR) | 27 Participants |
| Capecitabine | Number of Participants With Overall Response (OR) | 40 Participants |
95% CI: [7.6, 16.1]
95% CI: [12, 21.6]
p-value: 0.10995% CI: [-11.2, 1.1]Pearson Chi-Square Test
Secondary
Overall Survival (OS)
Average time from randomization to first documentation of death due to any cause.
Time frame: From time of randomization until death
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Overall Survival (OS) | 15.3 Months |
| Capecitabine | Overall Survival (OS) | 16.9 Months |
p-value: 0.21995% CI: [0.896, 1.611]Log Rank
Secondary
Time to Tumor Progression (TTP)
Time from randomization to first documentation of objective tumor progression.
Time frame: From time of randomization to every 6 weeks thereafter through 22 months
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Time to Tumor Progression (TTP) | 2.8 Months |
| Capecitabine | Time to Tumor Progression (TTP) | 4.2 Months |
p-value: <0.00195% CI: [1.188, 1.933]Log Rank
Secondary
Time to Tumor Response (TTR)
Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target lesions. PR was defined as a \>= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.
Time frame: From time of randomization to every 6 weeks thereafter through 22 months
Population: The study was stopped early for futility and TTR analysis was not performed.