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Trial record 1 of 1 for:    NCT00793546
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Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer

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ClinicalTrials.gov Identifier: NCT00793546
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : November 19, 2008
Results First Posted : November 5, 2012
Last Update Posted : November 5, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 29, 2008
First Posted Date  ICMJE November 19, 2008
Results First Submitted Date  ICMJE October 4, 2012
Results First Posted Date  ICMJE November 5, 2012
Last Update Posted Date November 5, 2012
Study Start Date  ICMJE February 2009
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2012)
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").
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2008)
To compare PFS assessed by an independent radiology vendor, of bosutinib in combination with exemestane versus exemestane alone as second line treatment for ER+/PgR+/ erbB2- advanced or metastatic breast cancer in postmenopausal women. [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2012)
  • 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 ]
    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 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").
  • Percentage of Participants With Objective Response [ Time Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ]
    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 Frame: Part 2 Baseline until death or up to 24 months ]
    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 Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ]
    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) [ Time Frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose ]
    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 [ Time Frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose ]
    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) [ Time Frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose ]
    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 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 ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2008)
To evaluate the safety profile of bosutinib-exemestane combo, to evaluate the combo PK, and exemestane alone PK, to evaluate efficacy parameters ORR, OS at 2 years, response duration, PFS, and to examine the health-related quality of life. [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Breast Cancer
Intervention  ICMJE
  • Drug: Bosutinib
    300 mg =(3x100mg) tablets once daily during the active phase of treatment until disease progression, unacceptable toxicity or withdrawal of consent occurs
  • Drug: exemestane
    25 mg tablet once daily
  • Drug: Exemestane
    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 Arms  ICMJE
  • Experimental: 1
    combination of bosutinib and exemestane
    Interventions:
    • Drug: Bosutinib
    • Drug: exemestane
  • Active Comparator: 2
    exemestane
    Intervention: Drug: Exemestane
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, Duvillié L, Láng 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 29, 2012)
42
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2008)
224
Actual Study Completion Date  ICMJE June 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   China,   Hong Kong,   Hungary,   India,   Poland,   South Africa,   Spain,   United States
Removed Location Countries Argentina,   Brazil,   France,   Korea, Republic of,   Netherlands,   Serbia,   Singapore,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00793546
Other Study ID Numbers  ICMJE 3160A6-2206
B1871009
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP