Clinical trial NCT00880009: Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer
Official title: A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB ADMINISTERED IN COMBINATION WITH LETROZOLE VS. LETROZOLE ALONE AS FIRST LINE THERAPY IN POST-MENOPAUSAL WOMEN WITH LOCALLY ADVANCED OR METASTATIC ER+/PR+/HER2- BREAST CANCER.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-04-13
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

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: Part 1 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 36 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, 24, 52, 2-6 weeks after the last dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0 hour (pre-dose) on Day 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; 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; 2, 3, 4, 6, 8, 24 hours post-dose on Day 29
Other outcomes:
Locations:
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates
state: Illinois
city: Niles
country: United States
facility: Oncology Specialists SC
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Wilrijk
country: Belgium
facility: AZ Sint-Augustinus
city: Beijing
country: China
facility: Cancer Hospital, Academy of Med Science and Peking Union Med
state: Beijing
city: Hong Kong
country: Hong Kong
facility: UNIMED Medical Institute
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly
city: Warszawa
country: Poland
facility: Centrum Medyczne Ostrobramska Niepubliczny Zaklad Opieki Zdr
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
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 letrozole: a phase II trial in postmenopausal women evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. Oncologist. 2014 Apr;19(4):348-9. doi: 10.1634/theoncologist.2014-0021. Epub 2014 Mar 27.