Study Evaluating SKI-606 (Bosutinib) In Subjects With Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Study Of SKI-606 In Subjects With Advanced Or Metastatic Breast Cancer

Conditions
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Breast Neoplasms, Neoplasm Metastasis

Intervention / Treatment
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* Drug: SKI-606 (Bosutinib)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced breast cancer<br> | Drug: SKI-606 (Bosutinib)<br>* SKI-606 (Bosutinib) 400mg once daily, for as long as tolerated or until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline up to Week 16 | 
| 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. | Baseline up to 30 days after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline up to Year 2 | 
| 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. | Baseline up to Year 1 | 
| 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. | Baseline up to end of treatment (Week 77) | 
| 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. | Baseline up to end of treatment (Week 77) | 
| 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. | Baseline up to end of treatment (Week 77) | 
| 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. | Baseline up to end of treatment (Week 77) | 
| 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. | Day 1 up to end of treatment (Week 77) | 
| 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. | Baseline, Weeks 1,4,8,12,16, every 8 weeks thereafter and 14 days after last dose of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Breast Cancer