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Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer

Primary Purpose

Advanced Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bosutinib
exemestane
Exemestane
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Breast Cancer focused on measuring Bosutinib, Exemestane, postmenopausal, breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Woman aged 18 years or older.
  • Confirmed pathologic diagnosis of breast cancer.
  • Locally advanced, metastatic, or locoregional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
  • Surgically sterile or postmenopausal woman.
  • Documented ER+ and/or PgR+ and erbB2- tumor.
  • Progression of locally advanced or metastatic disease during treatment with a nonsteroidal AI or tamoxifen, or progression during treatment with (or within 6 months of discontinuation of) an adjuvant nonsteroidal AI.

Exclusion Criteria:

  • Prior exemestane, prior bosutinib, or any other prior anti-Src therapy.
  • More than 1 prior endocrine treatment for locally advanced or MBC.
  • More than 1 prior cytotoxic chemotherapy regimen in metastatic setting.
  • Bone or skin as the only site of disease.

Sites / Locations

  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

combination of bosutinib and exemestane

exemestane

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) Based on Independent Radiologist
Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

Secondary Outcome Measures

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 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Progression Free Survival (PFS) Based on Investigator
Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Percentage of Participants With Objective Response
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to >=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.
Overall Survival (OS)
Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Duration of Response (DR)
Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B)
FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and additional concerns on breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures ranges from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL.
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) = worst imaginable health state to 100 mm =best imaginable health state; higher scores indicate a better health state.
Maximum Observed Plasma Concentration (Cmax)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).

Full Information

First Posted
October 29, 2008
Last Updated
October 4, 2012
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00793546
Brief Title
Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer
Official Title
A Phase 2, Randomized, Open-Label Study Of Bosutinib Administered In Combination With Exemestane Versus Exemestane Alone As Second Line Therapy In Postmenopausal Women With Locally Advanced Or Metastatic ER+/PgR+/ErbB2- Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
February 2009 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a phase 2, open-label, multicenter, 2-arm study of bosutinib administered in combination with exemestane versus exemestane alone. This is a 2-part study consisting of a safety lead-in phase and randomized phase 2 portion. Subjects in part 1 will receive bosutinib and exemestane daily, and will be closely monitored for 28 days. If no safety concerns arise, then future eligible subjects will be randomly assigned to the main phase of the study. They will either receive bosutinib daily combined with daily exemestane, or daily exemestane alone for a specified period of time. Subjects will be followed up for survival after treatment discontinuation.
Detailed Description
This study was terminated on 19 Apr 2010 due to unfavorable risk benefit ratio which did not support continuation in part 2 of the study. Even if the safety profile of the combination of Bosutinib and Exemestane was acceptable 25% of subjects had treatment related liver events including 14% of severe liver events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Breast Cancer
Keywords
Bosutinib, Exemestane, postmenopausal, breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
combination of bosutinib and exemestane
Arm Title
2
Arm Type
Active Comparator
Arm Description
exemestane
Intervention Type
Drug
Intervention Name(s)
Bosutinib
Intervention Description
300 mg =(3x100mg) tablets once daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs
Intervention Type
Drug
Intervention Name(s)
exemestane
Intervention Description
25 mg tablet once daily
Intervention Type
Drug
Intervention Name(s)
Exemestane
Intervention Description
25 mg - 1 tablet per day- once daily daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) Based on Independent Radiologist
Description
Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame
Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Secondary Outcome Measure Information:
Title
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
Description
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 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame
Baseline up to 28 days after the last dose
Title
Progression Free Survival (PFS) Based on Investigator
Description
Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame
Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Title
Percentage of Participants With Objective Response
Description
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to >=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.
Time Frame
Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Title
Overall Survival (OS)
Description
Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time Frame
Part 2 Baseline until death or up to 24 months
Title
Duration of Response (DR)
Description
Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame
Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Title
Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B)
Description
FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and additional concerns on breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures ranges from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL.
Time Frame
Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Title
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score
Description
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time Frame
Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Title
Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)
Description
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) = worst imaginable health state to 100 mm =best imaginable health state; higher scores indicate a better health state.
Time Frame
Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Title
Maximum Observed Plasma Concentration (Cmax)
Time Frame
0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame
0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
Description
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time Frame
0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Woman aged 18 years or older. Confirmed pathologic diagnosis of breast cancer. Locally advanced, metastatic, or locoregional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy. Surgically sterile or postmenopausal woman. Documented ER+ and/or PgR+ and erbB2- tumor. Progression of locally advanced or metastatic disease during treatment with a nonsteroidal AI or tamoxifen, or progression during treatment with (or within 6 months of discontinuation of) an adjuvant nonsteroidal AI. Exclusion Criteria: Prior exemestane, prior bosutinib, or any other prior anti-Src therapy. More than 1 prior endocrine treatment for locally advanced or MBC. More than 1 prior cytotoxic chemotherapy regimen in metastatic setting. Bone or skin as the only site of disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33461
Country
United States
Facility Name
Pfizer Investigational Site
City
Joliet
State/Province
Illinois
ZIP/Postal Code
60435
Country
United States
Facility Name
Pfizer Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Pfizer Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Pfizer Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
84202
Country
United States
Facility Name
Pfizer Investigational Site
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Pfizer Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Pfizer Investigational Site
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Facility Name
Pfizer Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4283
Country
United States
Facility Name
Pfizer Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Pfizer Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Pfizer Investigational Site
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Pfizer Investigational Site
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Pfizer Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Pfizer Investigational Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Pfizer Investigational Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Pfizer Investigational Site
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 5L3
Country
Canada
Facility Name
Pfizer Investigational Site
City
Beijing
ZIP/Postal Code
100021
Country
China
Facility Name
Pfizer Investigational Site
City
Hong Kong
Country
Hong Kong
Facility Name
Pfizer Investigational Site
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Pfizer Investigational Site
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India
Facility Name
Pfizer Investigational Site
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411001
Country
India
Facility Name
Pfizer Investigational Site
City
Olsztyn
ZIP/Postal Code
10-513
Country
Poland
Facility Name
Pfizer Investigational Site
City
Lynnwood
State/Province
Gauteng
ZIP/Postal Code
0081
Country
South Africa
Facility Name
Pfizer Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Pfizer Investigational Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Pfizer Investigational Site
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Pfizer Investigational Site

12. IPD Sharing Statement

Citations:
PubMed Identifier
24674873
Citation
Moy B, Neven P, Lebrun F, Bellet M, Xu B, Sarosiek T, Chow L, Goss P, Zacharchuk C, Leip E, Turnbull K, Bardy-Bouxin N, Duvillie L, Lang I. Bosutinib in combination with the aromatase inhibitor exemestane: a phase II trial in postmenopausal women with previously treated locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. Oncologist. 2014 Apr;19(4):346-7. doi: 10.1634/theoncologist.2014-0022. Epub 2014 Mar 27.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=3160A6-2206&StudyName=Study%20Evaluating%20Bosutinib-Exemestane%20Combination%20Vs%20Exemestane%20Alone%20in%20Post%20Menopausal%20Women%20With%20Breast%20Cancer
Description
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Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer

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