Clinical trial NCT00793546: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced Breast Cancer
Keywords: Bosutinib
Exemestane
postmenopausal
breast cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-11-19
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS) Based on Independent Radiologist
timeFrame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
Secondary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after the last dose
measure: Progression Free Survival (PFS) Based on Investigator
timeFrame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
measure: Percentage of Participants With Objective Response
timeFrame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
measure: Overall Survival (OS)
timeFrame: Part 2 Baseline until death or up to 24 months
measure: Duration of Response (DR)
timeFrame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
measure: Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B)
timeFrame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
measure: Euro Quality of Life (EQ-5D)- Health State Profile Utility Score
timeFrame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
measure: Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)
timeFrame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
timeFrame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Other outcomes:
Locations:
city: Lake Worth
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Joliet
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: New Brunswick
country: United States
facility: Pfizer Investigational Site
state: New Jersey
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Bethlehem
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
city: South Brisbane
country: Australia
facility: Pfizer Investigational Site
state: Queensland
city: Brussels
country: Belgium
facility: Pfizer Investigational Site
city: Leuven
country: Belgium
facility: Pfizer Investigational Site
city: Liege
country: Belgium
facility: Pfizer Investigational Site
city: Wilrijk
country: Belgium
facility: Pfizer Investigational Site
city: Kelowna
country: Canada
facility: Pfizer Investigational Site
state: British Columbia
city: Beijing
country: China
facility: Pfizer Investigational Site
city: Hong Kong
country: Hong Kong
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Mumbai
country: India
facility: Pfizer Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Pfizer Investigational Site
state: Maharashtra
city: Olsztyn
country: Poland
facility: Pfizer Investigational Site
city: Lynnwood
country: South Africa
facility: Pfizer Investigational Site
state: Gauteng
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Valencia
country: Spain
facility: Pfizer Investigational Site
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.