Breast Neoplasms, Neoplasm Metastasis
Conditions
Keywords
Advanced Breast Cancer
Brief summary
The purpose of this study is to determine if SKI-606 (Bosutinib) is effective in the treatment of advanced or metastatic breast cancer. Patients must have current Stage IIIB, IIIC or IV breast cancer and have progressed after 1 to 3 prior chemotherapy regimens.
Interventions
SKI-606 (Bosutinib) 400mg once daily, for as long as tolerated or until disease progression.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IIIB, IIIC or IV breast cancer not curable with available therapy. * Patients must have progressed after 1 but not more than 3 prior chemotherapy regimens. * Life expectancy of at least 16 weeks. * Ability to swallow whole capsules.
Exclusion criteria
* Use of or requirement for bisphosphonates within 8 weeks prior to screening. * Any other cancer within 5 years of screening, except for basal cell carcinoma or cervical carcinoma in situ * Uncontrolled cardiac disease including congestive heart failure, angina, heart attack, etc. * Recent or ongoing significant gastrointestinal disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | Baseline up to 30 days after last dose of study treatment | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. |
| Progression-Free Survival (PFS) Rate | Baseline up to Week 16 | PFS was based on Kaplan-Meier estimates. PFS was defined as time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from death case report forms (CRFs). Percentage of participants who had not experienced progression or death by Week 16 is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) | Baseline up to Year 1 | Percentage of participants with OR was based on the assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to sponsor modified Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions. Confirmed PR defined as more than or equal to (\>=) 30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response. |
| Percentage of Participants With Clinical Benefit | Baseline up to end of treatment (Week 77) | Clinical benefit was defined as a confirmed CR or PR, or stable disease (SD) for more than (\>) 24 weeks as the best response before the first evidence of progressive disease (PD). A participant demonstrating CR, PR, or SD \>24 weeks at any time while on study was counted in the numerator. |
| Number of Participants With Change From Baseline in Laboratory Test Results | Baseline up to end of treatment (Week 77) | Number of participants with potentially clinically significant (PCS) laboratory values are reported. Criteria for PCS laboratory values include: aspartate aminotransferase (AST), alanine aminotransferase (ALT) \>5\*upper limit of normal(ULN) milliunit/milliliter(mU/mL); total bilirubin \>3\*ULN micromole/L; sodium \<130, magnesium \<0.4 and \>1.23 millimole/L; lipase \>2\*ULN microkats/L; neutrophils \<1\*10\^9/L. Participants meeting at least 1 PCS criteria are reported. |
| Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations | Baseline up to end of treatment (Week 77) | Number of participants with potentially clinically significant (PCS) vital signs and physical examinations are reported. Criteria for PCS vital signs include: respiratory rate \>25 breaths/minute and PCS physical examinations include: an increase or decrease from baseline of \>=7% in body weight. |
| Concomitant Medications Used for Management of Adverse Events (AEs) | Day 1 up to end of treatment (Week 77) | Number of participants taking any non-study medications which were administered from Study Day 1 to last dose of study treatment (Week 77) as a management of an AE were to be reported. |
| Change From Baseline in Karnofsky Performance Status (KPS) at Week 1, 4, 8, 12, 16, Every 8 Weeks Thereafter and 14 Days After Last Dose of Study Treatment | Baseline, Weeks 1,4,8,12,16, every 8 weeks thereafter and 14 days after last dose of study treatment | KPS: 11 level score ranged 100 to 0, to assess functional impairment. 100:Normal; 90:Able to carry on normal activity; 80:Normal activity with effort, some signs or symptoms of disease; 70:Cares for self, unable to carry on normal activity or to do active work; 60:Requires occasional assistance but is able to care for most of needs; 50:Requires considerable assistance and frequent medical care; 40:Disabled,requires special care and assistance; 30:Severely disabled; hospitalization indicated although death is not imminent; 20:Very sick; 10:Morbibund,fatal processes progressing rapidly; 0:Death. |
| Number of Participants With Change From Baseline in Electrocardiogram (ECG) | Baseline up to end of treatment (Week 77) | Number of participants with potentially clinically significant (PCS) ECG findings are reported. Criteria for PCS ECG findings include: no sinus rhythm; heart rate \>=120 beats per minute (bpm) or increase \>=15 bpm; QT interval corrected using Bazett's formula (QTcB) \>60 milliseconds (msec) change from baseline; and overall ECG evaluation not normal. |
| Overall Survival (OS) | Baseline up to Year 2 | OS was estimated by Kaplan-Meier method. Survival was defined as the time period from the date of first dose of study treatment to the date of death, censored at the participant's last contact date. Percentage of participants who were still alive at 2 years is reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Population Pharmacokinetics (PK) | Pre-dose, 2, 7, 20 hours post-dose on Day 1 of Week 4 and pre-dose on Day 1 of Weeks 1, 8, 12, 16, and 24 | 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
Australia, France, Hong Kong, Malta, Poland, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bosutinib Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred. | 73 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 46 |
| Overall Study | Enrolled, Not Treated | 2 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Bosutinib |
|---|---|
| Age Continuous | 54.27 years STANDARD_DEVIATION 9.81 |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 70 / 73 |
| serious Total, serious adverse events | 24 / 73 |
Outcome results
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: Baseline up to 30 days after last dose of study treatment
Population: Safety population included all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | AEs | 97 percentage of participants |
| Bosutinib | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | SAEs | 33 percentage of participants |
Primary
Progression-Free Survival (PFS) Rate
PFS was based on Kaplan-Meier estimates. PFS was defined as time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from death case report forms (CRFs). Percentage of participants who had not experienced progression or death by Week 16 is reported.
Time frame: Baseline up to Week 16
Population: Intent-To-Treat (ITT) population included all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib | Progression-Free Survival (PFS) Rate | 39.6 percentage of participants |
Secondary
Change From Baseline in Karnofsky Performance Status (KPS) at Week 1, 4, 8, 12, 16, Every 8 Weeks Thereafter and 14 Days After Last Dose of Study Treatment
KPS: 11 level score ranged 100 to 0, to assess functional impairment. 100:Normal; 90:Able to carry on normal activity; 80:Normal activity with effort, some signs or symptoms of disease; 70:Cares for self, unable to carry on normal activity or to do active work; 60:Requires occasional assistance but is able to care for most of needs; 50:Requires considerable assistance and frequent medical care; 40:Disabled,requires special care and assistance; 30:Severely disabled; hospitalization indicated although death is not imminent; 20:Very sick; 10:Morbibund,fatal processes progressing rapidly; 0:Death.
Time frame: Baseline, Weeks 1,4,8,12,16, every 8 weeks thereafter and 14 days after last dose of study treatment
Population: Data for this pre-specified outcome was collected but not statistically summarized for analysis as there were no clinically significant changes observed.
Secondary
Concomitant Medications Used for Management of Adverse Events (AEs)
Number of participants taking any non-study medications which were administered from Study Day 1 to last dose of study treatment (Week 77) as a management of an AE were to be reported.
Time frame: Day 1 up to end of treatment (Week 77)
Population: Data for this pre-specified outcome measure was not statistically summarized for analysis, but collected and reported in individual participant listings as planned.
Secondary
Number of Participants With Change From Baseline in Electrocardiogram (ECG)
Number of participants with potentially clinically significant (PCS) ECG findings are reported. Criteria for PCS ECG findings include: no sinus rhythm; heart rate \>=120 beats per minute (bpm) or increase \>=15 bpm; QT interval corrected using Bazett's formula (QTcB) \>60 milliseconds (msec) change from baseline; and overall ECG evaluation not normal.
Time frame: Baseline up to end of treatment (Week 77)
Population: Safety population included all enrolled participants who received at least 1 dose of study treatment. Here N (Number of Participants Analyzed) represents number of participants who had at least 1 on-treatment assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib | Number of Participants With Change From Baseline in Electrocardiogram (ECG) | No sinus rhythm | 12 participants |
| Bosutinib | Number of Participants With Change From Baseline in Electrocardiogram (ECG) | Heart Rate (>=120 bpm and increase >=15bpm) | 2 participants |
| Bosutinib | Number of Participants With Change From Baseline in Electrocardiogram (ECG) | QTcB Interval (>60 msec change from baseline) | 1 participants |
| Bosutinib | Number of Participants With Change From Baseline in Electrocardiogram (ECG) | Overall ECG not normal | 12 participants |
Secondary
Number of Participants With Change From Baseline in Laboratory Test Results
Number of participants with potentially clinically significant (PCS) laboratory values are reported. Criteria for PCS laboratory values include: aspartate aminotransferase (AST), alanine aminotransferase (ALT) \>5\*upper limit of normal(ULN) milliunit/milliliter(mU/mL); total bilirubin \>3\*ULN micromole/L; sodium \<130, magnesium \<0.4 and \>1.23 millimole/L; lipase \>2\*ULN microkats/L; neutrophils \<1\*10\^9/L. Participants meeting at least 1 PCS criteria are reported.
Time frame: Baseline up to end of treatment (Week 77)
Population: Safety population included all enrolled participants who received at least 1 dose of study treatment. Here N (Number of Participants Analyzed) represents number of participants who had at least 1 on-treatment assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | Total Bilirubin (>3*ULN) | 1 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | ALT (>5*ULN) | 12 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | AST (>5*ULN) | 10 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | Lipase (>2*ULN) | 1 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | Neutrophils (<1*10^9/L) | 1 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 2 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | Magnesium (<0.4 mmol/L) | 3 participants |
| Bosutinib | Number of Participants With Change From Baseline in Laboratory Test Results | Magnesium (>1.23 mmol/L) | 3 participants |
Secondary
Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations
Number of participants with potentially clinically significant (PCS) vital signs and physical examinations are reported. Criteria for PCS vital signs include: respiratory rate \>25 breaths/minute and PCS physical examinations include: an increase or decrease from baseline of \>=7% in body weight.
Time frame: Baseline up to end of treatment (Week 77)
Population: Safety population included all enrolled participants who received at least 1 dose of study treatment. Here N (Number of Participants Analyzed) represents number of participants who had at least 1 on-treatment assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib | Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations | Respiratory Rate (> 25 breaths/minute) | 6 participants |
| Bosutinib | Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations | Weight (decrease >=7%) | 9 participants |
| Bosutinib | Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations | Weight (increase >=7%) | 1 participants |
| Bosutinib | Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations | Ophthalmological examinations | 0 participants |
Secondary
Overall Survival (OS)
OS was estimated by Kaplan-Meier method. Survival was defined as the time period from the date of first dose of study treatment to the date of death, censored at the participant's last contact date. Percentage of participants who were still alive at 2 years is reported.
Time frame: Baseline up to Year 2
Population: ITT population included all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib | Overall Survival (OS) | 26.4 percentage of participants |
Secondary
Percentage of Participants With Clinical Benefit
Clinical benefit was defined as a confirmed CR or PR, or stable disease (SD) for more than (\>) 24 weeks as the best response before the first evidence of progressive disease (PD). A participant demonstrating CR, PR, or SD \>24 weeks at any time while on study was counted in the numerator.
Time frame: Baseline up to end of treatment (Week 77)
Population: ITT population included all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib | Percentage of Participants With Clinical Benefit | 27.4 percentage of participants |
Secondary
Percentage of Participants With Objective Response (OR)
Percentage of participants with OR was based on the assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to sponsor modified Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions. Confirmed PR defined as more than or equal to (\>=) 30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.
Time frame: Baseline up to Year 1
Population: ITT population included all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib | Percentage of Participants With Objective Response (OR) | 5.5 percentage of participants |
Other Pre-specified
Population Pharmacokinetics (PK)
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: Pre-dose, 2, 7, 20 hours post-dose on Day 1 of Week 4 and pre-dose on Day 1 of Weeks 1, 8, 12, 16, and 24