Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00880009
First received: April 8, 2009
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

This is a phase 2 study of bosutinib administered in combination with letrozole versus letrozole alone in post-menopausal women with breast cancer. This is a 2-part study. Subjects in part 1 will receive bosutinib and letrozole daily, and will be closely monitored for 28 days. The second part will proceed with subjects receiving a dose that is determined to be safe based on the safety evaluation of the first part. Eligible subjects will be randomly assigned to receive either bosutinib daily combined with daily letrozole, or daily letrozole alone for a specified period of time. Subjects will be followed up for survival after study drug discontinuation.


Condition Intervention Phase
Breast Cancer
Drug: Bosutinib
Drug: Letrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-Label Study Of Bosutinib Administered In Combination With Letrozole Versus Letrozole Alone As First Line Therapy In Post-Menopausal Women With Locally Advanced Or Metastatic ER+/PgR+/ErbB2- Breast Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Time in weeks from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: 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"). PFS assessed by independent radiologist was to be reported.


Secondary Outcome Measures:
  • Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part 1 Baseline up to 28 days after the last dose ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Time in weeks from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS: calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression: determined from oncologic assessment data (where data meet the criteria for PD), or from AE data (where the outcome was "Death"). PFS assessed by investigator was to be reported.

  • Percentage of Participants With Objective Response [ Time Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
    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 36 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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, 24, 52, 2-6 weeks after the last dose ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 hour (pre-dose) on Day 1; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 hour (pre-dose) on Day 1; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] [ Time Frame: 0 hour (pre-dose) on Day 1; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29 ] [ Designated as safety issue: No ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).


Enrollment: 16
Study Start Date: July 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Combination of Bosutinib and Letrozole
Drug: Bosutinib
400mg (4x100)mg tablets once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs
Drug: Letrozole
2.5 mg - one tablet per day- once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs
Active Comparator: 2
Letrozole
Drug: Letrozole
2.5 mg - one tablet per day- once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs

Detailed Description:

This study was terminated on 19 April 2009 due to unfavorable risk benefit ratio of Bosutinib in combination with Letrozole including one confirmed Hy's law case. 37.5% of patients had treatment related liver events with the majority of severe events resulting in permanent study treatment discontinuation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Surgically sterile or post-menopausal women.
  • Confirmed pathologic diagnosis of breast cancer.
  • Locally advanced or metastatic, or loco-regional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
  • Documented ER+ and/or PgR+ and erbB2- tumor based on most recently analyzed biopsy, as documented by a local laboratory.
  • At least 1 radiologically measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

  • Prior letrozole (except in adjuvant setting), prior bosutinib, or any other prior Src inhibitor.
  • Prior endocrine treatment for locally advanced or metastatic breast cancer (up to one prior adjuvant Aromatase Inhibitor (AI) agent/regimen is permitted).
  • More than 1 prior chemotherapy regimen in locally advanced or metastatic breast cancer.
  • Adjuvant endocrine therapy <=12 months prior to day 1 of treatment.
  • Disease refractory (ie, Progressive disease (PD) within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
  • Bone or skin as the only site of disease.
  • Extensive visceral disease or active Central Nervous System (CNS) disease.
  • Any other cancer within 5 years of screening with the exception of ER+ contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
  • Major surgery or radiotherapy within 14 days of treatment day.
  • Inadequate hepatic/renal/bone marrow function.
  • History of clinically significant or uncontrolled cardiac disease.
  • Serious concurrent illness.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00880009

Locations
United States, California
Pfizer Investigational Site
Whittier, California, United States, 90603
United States, Illinois
Pfizer Investigational Site
Joliet, Illinois, United States, 60435
Pfizer Investigational Site
Niles, Illinois, United States, 60714
United States, Massachusetts
Pfizer Investigational Site
Boston, Massachusetts, United States, 02114
United States, Michigan
Pfizer Investigational Site
Detroit, Michigan, United States, 84202
Belgium
Pfizer Investigational Site
Wilrijk, Belgium, 2610
China, Beijing
Pfizer Investigational Site
Beijing, Beijing, China, 100021
Hong Kong
Pfizer Investigational Site
Hong Kong, Hong Kong
Hungary
Pfizer Investigational Site
Budapest, Hungary, 1122
Poland
Pfizer Investigational Site
Warszawa, Poland, 04125
Singapore
Pfizer Investigational Site
Singapore, Singapore, 308433
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00880009     History of Changes
Other Study ID Numbers: 3160A6-2207, B1871010
Study First Received: April 8, 2009
Results First Received: October 4, 2012
Last Updated: October 4, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014