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

• ClinicalTrials.gov Identifier: NCT00319254
• Recruitment Status: Completed
• First Posted: April 27, 2006
• Results First Posted: January 31, 2013
• Last Update Posted: January 31, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms; Neoplasm Metastasis	Drug: SKI-606 (Bosutinib)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study Of SKI-606 In Subjects With Advanced Or Metastatic Breast Cancer
• Study Start Date: May 2006
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Advanced breast cancer	Drug: SKI-606 (Bosutinib); SKI-606 (Bosutinib) 400mg once daily, for as long as tolerated or until disease progression.

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) Rate [ Time Frame: 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.
2. Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) [ Time Frame: 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.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 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.
2. Percentage of Participants With Objective Response (OR) [ Time Frame: 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.
3. Percentage of Participants With Clinical Benefit [ Time Frame: 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.
4. Number of Participants With Change From Baseline in Laboratory Test Results [ Time Frame: 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.
5. Number of Participants With Change From Baseline in Electrocardiogram (ECG) [ Time Frame: 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.
6. Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations [ Time Frame: 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.
7. Concomitant Medications Used for Management of Adverse Events (AEs) [ Time Frame: 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.
8. 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 [ Time Frame: 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.

Other Outcome Measures:

1. Population Pharmacokinetics (PK) [ 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Pfizer Investigational Site

Duarte, California, United States, 91010-3000

Pfizer Investigational Site

Santa Monica, California, United States, 90404

United States, Florida

Pfizer Investigational Site

Tampa, Florida, United States, 33612

United States, Ohio

Pfizer Investigational Site

Cleveland, Ohio, United States, 44195

Australia, New South Wales

Pfizer Investigational Site

Darlinghurst, New South Wales, Australia, 2010

France

Pfizer Investigational Site

Dijon, France, 21034

Pfizer Investigational Site

Saint-Herblain, France, 44805

Hong Kong

Pfizer Investigational Site

Pokfulam, Hong Kong

Malta

Pfizer Investigational Site

Floriana, Malta, VLT 14

Poland

Pfizer Investigational Site

Lodz, Poland, 90-553

Pfizer Investigational Site

Wroclaw, Poland, 51-124

Russian Federation

Pfizer Investigational Site

Moscow, Russian Federation, 115478

Ukraine

Pfizer Investigational Site

Dnipropetrovsk, Ukraine, 49102

Pfizer Investigational Site

Sumy, Ukraine, 40005

Pfizer Investigational Site

Uzhgorod, Ukraine, 88014

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00319254
• Other Study ID Numbers: 3160A2-201; B1871014
• First Posted: April 27, 2006
• Results First Posted: January 31, 2013
• Last Update Posted: January 31, 2013
• Last Verified: December 2012

Keywords provided by Pfizer:

Advanced Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms; Neoplasm Metastasis; Neoplasms by Site; Breast Diseases; Skin Diseases; Neoplastic Processes; Pathologic Processes