Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: Bosutinib; Drug: exemestane; Drug: Exemestane

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: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• • • Pfizer Investigational Site
• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Pfizer Investigational Site
• Belgium
  • Brussels, Belgium, 1000
    • Pfizer Investigational Site
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
  • Liege, Belgium, 4000
    • Pfizer Investigational Site
  • Wilrijk, Belgium, 2610
    • Pfizer Investigational Site
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Pfizer Investigational Site
• China
  • Beijing, China, 100021
    • Pfizer Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Pfizer Investigational Site
• Hungary
  • Budapest, Hungary, 1122
    • Pfizer Investigational Site
• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Pfizer Investigational Site
    • Pune, Maharashtra, India, 411001
      • Pfizer Investigational Site
• Poland
  • Olsztyn, Poland, 10-513
    • Pfizer Investigational Site
• South Africa
  • Gauteng
    • Lynnwood, Gauteng, South Africa, 0081
      • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Pfizer Investigational Site
  • Madrid, Spain, 28040
    • Pfizer Investigational Site
  • Valencia, Spain, 46010
    • Pfizer Investigational Site
• United States
  • Florida
    • Lake Worth, Florida, United States, 33461
      • Pfizer Investigational Site
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 84202
      • Pfizer Investigational Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10032
      • Pfizer Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; combination of bosutinib and exemestane	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
Active Comparator: 2; exemestane	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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").	Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose
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.	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.	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").	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).	Part 2 Baseline until death or up to 24 months
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.	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.	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.	Part 2 Baseline, Week 12, 2 to 6 weeks after last dose
Maximum Observed Plasma Concentration (Cmax)		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)		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).	0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: November 17, 2008
• First Posted (Estimate): November 19, 2008

Study Record Updates

• Last Update Posted (Estimate): November 4, 2012
• Last Update Submitted That Met QC Criteria: October 4, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: breast cancer; postmenopausal; Bosutinib; Exemestane
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: 3160A6-2206; B1871009