Advanced Breast CancerPhase 2NCT00793546
Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer
A Phase 2 study testing Bosutinib and exemestane in people with Advanced Breast Cancer, run by Pfizer at 28 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- Bosutinib and exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 28 sitesin 12 countries
- Study dates
- Feb 2009to Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
28 sites in 12 countries.
28 sites in 12 countries
United States11 sites
Pfizer Investigational Site
Bethlehem, Pennsylvania, 18015
Pfizer Investigational Site
Boston, Massachusetts, 02114
Pfizer Investigational Site
Boston, Massachusetts, 02115
Pfizer Investigational Site
Detroit, Michigan, 84202
Pfizer Investigational Site
Joliet, Illinois, 60435
Pfizer Investigational Site
Lake Worth, Florida, 33461
Pfizer Investigational Site
New Brunswick, New Jersey, 08901
Pfizer Investigational Site
New York, New York, 10032
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19104-4283
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19104
Pfizer Investigational Site
Seattle, Washington, 98104
Belgium4 sites
Pfizer Investigational Site
Brussels, Brussels Capital, 1000
Pfizer Investigational Site
Leuven, Leuven, 3000
Pfizer Investigational Site
Liège, Liege, 4000
Pfizer Investigational Site
Wilrijk, 2610
Spain3 sites
Pfizer Investigational Site
Barcelona, Barcelona, 08035
Pfizer Investigational Site
Madrid, Madrid, 28040
Pfizer Investigational Site
Valencia, Valencia, 46010
India2 sites
Pfizer Investigational Site
Mumbai, Maharashtra, 400012
Pfizer Investigational Site
Pune, Maharashtra, 411001
Australia1 site
Pfizer Investigational Site
South Brisbane, Queensland, 4101
Location not given1 site
Pfizer Investigational Site
About this study
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
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.
Read the 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.
- Conditions
- Advanced Breast Cancer
- Being tested
- Bosutinib, exemestane
- Keywords
- Bosutinib, Exemestane, postmenopausal, breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosutinibDrug
300 mg =(3x100mg) tablets once daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs
exemestaneDrug
25 mg tablet once daily
ExemestaneDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | combination of bosutinib and exemestane Receives: Drug: Bosutinib; Drug: exemestane |
| 2 | Active comparator | exemestane Receives: Drug: Exemestane |
What is being measured
The primary outcome is the main question the study is designed to answer.
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").
Measured: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Secondary outcomes (11)
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.
Measured: Baseline up to 28 days after the last dose
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").
Measured: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
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.
Measured: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
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).
Measured: Part 2 Baseline until death or up to 24 months
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.
Measured: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
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.
Measured: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
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.
Measured: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
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.
Measured: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Maximum Observed Plasma Concentration (Cmax)
Measured: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measured: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
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).
Measured: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2008 (estimated)
- Study startFeb 2009
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00793546
- Sponsor's protocol ID
- 3160A6-2206
- Other IDs
- B1871009
- Status last verified
- Oct 2012
- First submitted
- 29 Oct 2008
- Last updated
- 5 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24674873
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00793546
- Acronym / sponsor ID
- 3160A6-2206
- Conditions
- Advanced Breast Cancer
- Keywords
- Bosutinib, Exemestane, postmenopausal, breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 42 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 19 Nov 2008 (estimated)
- Results
- Posted 5 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Bosutinib, Drug: exemestanecombination of bosutinib and exemestane |
| 2 | Active comparator | Drug: Exemestaneexemestane |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bosutinib300 mg =(3x100mg) tablets once daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs | Drug | 1 |
| exemestane25 mg tablet once daily | Drug | 1 |
| Exemestane25 mg - 1 tablet per day- once daily daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs | Drug | 2 |
Primary outcome
Progression Free Survival (PFS) Based on Independent Radiologist
Time frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
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").
11 secondary outcomes
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
Time frame: Baseline up to 28 days after the last dose
Progression Free Survival (PFS) Based on Investigator
Time frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Percentage of Participants With Objective Response
Time frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Overall Survival (OS)
Time frame: Part 2 Baseline until death or up to 24 months
Duration of Response (DR)
Time frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B)
Time frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score
Time frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)
Time frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
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
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
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
Time frame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24674873Moy 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
28 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bosutinib and exemestane in people with Advanced Breast Cancer, run by Pfizer at 28 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Belgium, Spain, India, Australia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) Based on Independent Radiologist (time frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00793546, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2012.