Clinical trial NCT00767520: Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer
Official title: A Randomized, Double-Blind, Multi-Center Phase II Trial of Exemestane (AromasinÂ®) Plus Dasatinib Versus Exemestane Plus Placebo in Advanced Estrogen Receptor-Positive Breast Cancer After Disease Progression on a Non-Steroidal Aromatase Inhibitor (NSAI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Advanced Estrogen Receptor Positive Breast Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-10-07
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether exemestane plus dasatinib will be well-tolerated and will increase progression-free survival (PFS) in the treatment of advanced estrogen-receptor positive (ER+) breast cancer after disease progression (PD) on a non-steroidal aromatase inhibitor (NSAI).


Eligibility criteria: Inclusion Criteria:

* Histologically-documented invasive estrogen receptor positive breast cancer , with tumor tissue from prior surgery available for analysis
* Prior therapy with a non-steroidal aromatase inhibitor
* Recurrent or progressive advanced breast cancer (locally-advanced or metastatic)
* Documented breast cancer with tumor ≤ 28 days prior to study entry
* Women who are NOT of childbearing potential
* Must be able to take oral medication
* Performance Status 0 or 1

Exclusion Criteria:

* Pleural or pericardial effusion or ascites (of any etiology; Grade ≥ 1) within 6 months prior to study entry
* Any chemotherapy, immunotherapy \< 6 months before study entry. Any targeted therapy (eg. lapatinib) \< 6 months before study entry, unless given in combination with an NSAI
* Any antitumor therapy, including radiotherapy or hormonal therapy, within 15 days prior to study entry
* Prior exposure to exemestane, any Src-family kinase inhibitor including dasatinib, to agents intended to control osteolytic disease other than bisphosphonates, or to any investigational agent for breast cancer
* Concurrent or previous malignant disease requiring chemotherapy or radiation treatment within the prior 3 years
* Significant bleeding disorder, or ongoing or recent clinically-significant gastrointestinal bleeding
* Any serious cardiac condition, including congestive heart failure or myocardial infarction within 6 months, uncontrolled angina, or Class III or IV heart disease as defined by the New York Heart Association, baseline ejection fraction ≤ 40%, diagnosed congenital long QT syndrome, clinically-significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes), QTc interval \> 450 msec at baseline (Fridericia correction)
* Hematologic abnormality Grade ≥ 2
* Hypocalcemia of Grade ≥ 1
* Any Chemistry abnormality of Grade ≥ 2 \[except Grade 2 indirect bilirubin permitted if diagnosed Gilbert's disease\]
* Pregnant Women and Women of Childbearing Potential (WOCBP)
* Extremely lactose intolerant, in the judgment of treating physician (100 mg dasatinib contains 135 mg lactose, posing a problem only if intolerance is severe)
* Receiving any of the following concomitant medications: Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Subjects must discontinue drug use at least 7 days prior to starting dasatinib)
* Potent inhibitors of CYP3A4 isoenzyme
* Prisoners or subjects who are involuntarily incarcerated; or subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Primary outcomes:
measure: Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo
timeFrame: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)
measure: Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo
timeFrame: Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)
Secondary outcomes:
measure: Number of Participants With Best Overall Response
timeFrame: at 6 months
measure: Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months
timeFrame: at 6 months
measure: Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
timeFrame: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)
measure: Participants With Freedom-From-Progression (FFP) at 6 Months
timeFrame: at 6 months
measure: Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
timeFrame: Prior to study therapy, at 8 week intervals until CR or PR. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer
measure: Duration of Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
timeFrame: Prior to study therapy, at 8 week intervals. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer.
measure: Changes in Participant-reported Pain Intensity in Participants With Bone Metastasis
timeFrame: Start of study, at treatment start, after 2, 4, and 8 weeks of therapy and every 8 weeks thereafter, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.
measure: Changes in Markers of Bone Lysis in Participants With Bone Metastasis
timeFrame: Screening, Day 1, after week 2, 4, and week 8 and subsequently every 8 weeks, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.
measure: Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs (as Per National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0)
timeFrame: From start of study drug therapy up to 30 days after the last dose. Median duration of therapy (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
measure: Number of Participants With Grade 1-4 Hematology Abnormalities (as Per the NCI CTCAE, Version 3.0)
timeFrame: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
measure: Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Bilirubin, Calcium, Creatinine, and Albumin (as Per the NCI CTCAE, Version 3.0)
timeFrame: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
measure: Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Potassium, Magnesium, Sodium, Phosphorous, Uric Acid, and Bicarbonate (as Per the NCI CTCAE, Version 3.0)
timeFrame: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
measure: Number of Participants With Abnormalities in Vital Signs
timeFrame: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.
measure: Number of Participants With Abnormalities in Electrocardiograms
timeFrame: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group, Inc
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group Inc
state: California
city: Philadelphia
country: United States
facility: Pennsylvania Oncology/Hematology Associates
state: Pennsylvania
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Hradec Kralove
country: Czech Republic
facility: Local Institution
city: Prague 5
country: Czech Republic
facility: Local Institution
city: Lille
country: France
facility: Local Institution
city: Paris Cedex 13
country: France
facility: Local Institution
city: Saint-Cloud Cedex
country: France
facility: Local Institution
city: Dublin
country: Ireland
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Opole
country: Poland
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Torrevieja
country: Spain
facility: Local Institution
city: Vasteras
country: Sweden
facility: Local Institution
city: Chelmsford
country: United Kingdom
facility: Local Institution
state: Essex
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Coventry
country: United Kingdom
facility: Local Institution
state: Warwickshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: