Back to resultsStudy Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer
Primary Purpose
Breast Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bosutinib
Letrozole
Letrozole
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Surgically sterile or post-menopausal women.
- Confirmed pathologic diagnosis of breast cancer.
- Locally advanced or metastatic, or loco-regional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
- Documented ER+ and/or PgR+ and erbB2- tumor based on most recently analyzed biopsy, as documented by a local laboratory.
- At least 1 radiologically measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Exclusion Criteria:
- Prior letrozole (except in adjuvant setting), prior bosutinib, or any other prior Src inhibitor.
- Prior endocrine treatment for locally advanced or metastatic breast cancer (up to one prior adjuvant Aromatase Inhibitor (AI) agent/regimen is permitted).
- More than 1 prior chemotherapy regimen in locally advanced or metastatic breast cancer.
- Adjuvant endocrine therapy <=12 months prior to day 1 of treatment.
- Disease refractory (ie, Progressive disease (PD) within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
- Bone or skin as the only site of disease.
- Extensive visceral disease or active Central Nervous System (CNS) disease.
- Any other cancer within 5 years of screening with the exception of ER+ contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
- Major surgery or radiotherapy within 14 days of treatment day.
- Inadequate hepatic/renal/bone marrow function.
- History of clinically significant or uncontrolled cardiac disease.
- Serious concurrent illness.
Sites / Locations
- American Institute of Research
- Joliet Oncology Hematology Associates
- Oncology Specialists SC
- Massachusetts General Hospital
- Henry Ford Health System
- AZ Sint-Augustinus
- Cancer Hospital, Academy of Med Science and Peking Union Med
- UNIMED Medical Institute
- Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly
- Centrum Medyczne Ostrobramska Niepubliczny Zaklad Opieki Zdr
- Johns Hopkins Singapore International Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
1
2
Arm Description
Combination of Bosutinib and Letrozole
Letrozole
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) Based on Independent Radiologist
Time in weeks from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: 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"). PFS assessed by independent radiologist was to be reported.
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 date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: determined from oncologic assessment data (where data meet the criteria for PD), or from AE data (where the outcome was "Death"). PFS assessed by investigator was to be reported.
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.
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
1. Study Identification
Unique Protocol Identification Number
NCT00880009
Brief Title
Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer
Official Title
A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB ADMINISTERED IN COMBINATION WITH LETROZOLE VS. LETROZOLE ALONE AS FIRST LINE THERAPY IN POST-MENOPAUSAL WOMEN WITH LOCALLY ADVANCED OR METASTATIC ER+/PR+/HER2- BREAST CANCER.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
July 30, 2009 (Actual)
Primary Completion Date
May 31, 2010 (Actual)
Study Completion Date
May 31, 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 study of bosutinib administered in combination with letrozole versus letrozole alone in post-menopausal women with breast cancer. This is a 2-part study. Subjects in part 1 will receive bosutinib and letrozole daily, and will be closely monitored for 28 days. The second part will proceed with subjects receiving a dose that is determined to be safe based on the safety evaluation of the first part. Eligible subjects will be randomly assigned to receive either bosutinib daily combined with daily letrozole, or daily letrozole alone for a specified period of time. Subjects will be followed up for survival after study drug discontinuation.
Detailed Description
This study was terminated on 19 April 2009 due to unfavorable risk benefit ratio of Bosutinib in combination with Letrozole including one confirmed Hy's law case. 37.5% of patients had treatment related liver events with the majority of severe events resulting in permanent study treatment discontinuation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Combination of Bosutinib and Letrozole
Arm Title
2
Arm Type
Active Comparator
Arm Description
Letrozole
Intervention Type
Drug
Intervention Name(s)
Bosutinib
Intervention Description
400mg (4x100)mg tablets once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
2.5 mg - one tablet per day- once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
2.5 mg - one tablet per day- once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) Based on Independent Radiologist
Description
Time in weeks from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: 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"). PFS assessed by independent radiologist was to be reported.
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
Part 1 Baseline up to 28 days after the last dose
Title
Progression-Free Survival (PFS) Based on Investigator
Description
Time in weeks from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: determined from oncologic assessment data (where data meet the criteria for PD), or from AE data (where the outcome was "Death"). PFS assessed by investigator was to be reported.
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 36 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, 24, 52, 2-6 weeks after the last dose
Title
Maximum Observed Plasma Concentration (Cmax)
Time Frame
0 hour (pre-dose) on Day 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; 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; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Surgically sterile or post-menopausal women.
Confirmed pathologic diagnosis of breast cancer.
Locally advanced or metastatic, or loco-regional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
Documented ER+ and/or PgR+ and erbB2- tumor based on most recently analyzed biopsy, as documented by a local laboratory.
At least 1 radiologically measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Exclusion Criteria:
Prior letrozole (except in adjuvant setting), prior bosutinib, or any other prior Src inhibitor.
Prior endocrine treatment for locally advanced or metastatic breast cancer (up to one prior adjuvant Aromatase Inhibitor (AI) agent/regimen is permitted).
More than 1 prior chemotherapy regimen in locally advanced or metastatic breast cancer.
Adjuvant endocrine therapy <=12 months prior to day 1 of treatment.
Disease refractory (ie, Progressive disease (PD) within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
Bone or skin as the only site of disease.
Extensive visceral disease or active Central Nervous System (CNS) disease.
Any other cancer within 5 years of screening with the exception of ER+ contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
Major surgery or radiotherapy within 14 days of treatment day.
Inadequate hepatic/renal/bone marrow function.
History of clinically significant or uncontrolled cardiac disease.
Serious concurrent illness.
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
American Institute of Research
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Joliet Oncology Hematology Associates
City
Joliet
State/Province
Illinois
ZIP/Postal Code
60435
Country
United States
Facility Name
Oncology Specialists SC
City
Niles
State/Province
Illinois
ZIP/Postal Code
60714
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
84202
Country
United States
Facility Name
AZ Sint-Augustinus
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Cancer Hospital, Academy of Med Science and Peking Union Med
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Facility Name
UNIMED Medical Institute
City
Hong Kong
Country
Hong Kong
Facility Name
Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Centrum Medyczne Ostrobramska Niepubliczny Zaklad Opieki Zdr
City
Warszawa
ZIP/Postal Code
04125
Country
Poland
Facility Name
Johns Hopkins Singapore International Medical Centre
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
24674874
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 letrozole: a phase II trial in postmenopausal women evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. Oncologist. 2014 Apr;19(4):348-9. doi: 10.1634/theoncologist.2014-0021. Epub 2014 Mar 27.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=3160A6-2207&StudyName=Study%20Evaluating%20Bosutinib-Letrozole%20Combination%20Versus%20Letrozole%20Alone%20In%20Post%20Menopausal%20Women%20With%20Breast%20Cancer
Description
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Learn more about this trial
Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer
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