A Phase 2 interventional study of Bosutinib and exemestane in Advanced Breast Cancer, sponsored by Pfizer. Terminated at 28 sites in 11 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-11-04.
Sponsored by Pfizer · Phase 2, Interventional, and Treatment
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 42 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
combination of bosutinib and exemestane
Drug: Bosutinib · Drug: exemestane
exemestane
Drug: Exemestane
300 mg =(3x100mg) tablets once daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs
25 mg tablet once daily
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
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").
Time frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
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.
Time frame: 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").
Time frame: 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.
Time frame: 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).
Time frame: 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.
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)
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
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.
Time frame: 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.
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)]
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
| Milestone | Bosutinib 400 mg + Exemestane 25 mg (Part 1) | Bosutinib 300 mg + Exemestane 25 mg (Part 1) |
|---|---|---|
| Started | 14 | 28 |
| Completed | 0 | 0 |
| Not completed | 14 | 28 |
| Withdrew: Death | 3 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Withdrew: Study terminated by sponsor | 8 | 27 |
| Withdrew: Other | 1 | 0 |
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").
No measurements were reported for this outcome.
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.
| percentage of participants | Bosutinib 400 mg + Exemestane 25 mg (Part 1) | Bosutinib 300 mg + Exemestane 25 mg (Part 1) |
|---|---|---|
| AEs | 100 | 96.4 |
| SAEs | 28.6 | 17.9 |
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").
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bosutinib 400 mg + Exemestane 25 mg (Part 1) | — | 4/14 (28.6%) | 14/14 (100%) |
| Bosutinib 300 mg + Exemestane 25 mg (Part 1) | — | 5/28 (17.9%) | 27/28 (96.4%) |
| Event | Bosutinib 400 mg + Exemestane 25 mg (Part 1) | Bosutinib 300 mg + Exemestane 25 mg (Part 1) |
|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 1/14 | 0/28 |
| Cardiac arrestCardiac disorders | 1/14 | 0/28 |
| Cardiac failureCardiac disorders | 1/14 | 0/28 |
| DiarrheaGastrointestinal disorders | 1/14 | 1/28 |
| Electrolyte imbalanceMetabolism and nutrition disorders | 1/14 | 0/28 |
| Fluid overloadMetabolism and nutrition disorders | 1/14 | 0/28 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/14 | 0/28 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 1/14 | 2/28 |
| General physical health deteriorationGeneral disorders | 0/14 | 1/28 |
| PneumoniaInfections and infestations | 0/14 | 1/28 |
| Event | Bosutinib 400 mg + Exemestane 25 mg (Part 1) | Bosutinib 300 mg + Exemestane 25 mg (Part 1) |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 12/14 | 15/28 |
| NauseaGastrointestinal disorders | 11/14 | 15/28 |
| VomitingGastrointestinal disorders | 8/14 | 12/28 |
| ConstipationGastrointestinal disorders | 1/14 | 9/28 |
| FatigueGeneral disorders | 4/14 | 6/28 |
| Alanine aminotransferase increasedInvestigations | 4/14 | 7/28 |
| Decreased appetiteMetabolism and nutrition disorders | 1/14 | 8/28 |
| RashSkin and subcutaneous tissue disorders | 4/14 | 4/28 |
| AstheniaGeneral disorders | 3/14 | 3/28 |
| Aspartate aminotransferase increasedInvestigations | 3/14 | 4/28 |
| Age Continuous(years) | Bosutinib 400 mg + Exemestane 25 mg (Part 1) | Bosutinib 300 mg + Exemestane 25 mg (Part 1) | Total |
|---|---|---|---|
| Mean | 64.1 ± 8.16 | 58.2 ± 10.02 | 60.2 ± 9.75 |
| Sex: Female, Male(Participants) | Bosutinib 400 mg + Exemestane 25 mg (Part 1) | Bosutinib 300 mg + Exemestane 25 mg (Part 1) | Total |
|---|---|---|---|
| Female | 14 | 28 | 42 |
| Male | 0 | 0 | 0 |
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