Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00767520
• Date of registration: 06/10/2008
• Primary sponsor: Bristol-Myers Squibb
• Public title: Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer
• Scientific title: A Randomized, Double-Blind, Multi-Center Phase II Trial of Exemestane (Aromasin®) Plus Dasatinib Versus Exemestane Plus Placebo in Advanced Estrogen Receptor-Positive Breast Cancer After Disease Progression on a Non-Steroidal Aromatase Inhibitor (NSAI)
• Date of first enrolment: April 2004
• Target sample size: 157
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00767520
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Countries of recruitment

Czech Republic, France, Ireland, Italy, Korea, Republic of, Norway, Poland, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Exemestane + Dasatinib

Drug: Exemestane + Placebo

Primary Outcome(s)

Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo [Time Frame: Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)]

Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo [Time Frame: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)]

Secondary Outcome(s)

Changes in Markers of Bone Lysis in Participants With Bone Metastasis [Time Frame: 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.]

Changes in Participant-reported Pain Intensity in Participants With Bone Metastasis [Time Frame: 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.]

Duration of Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms [Time Frame: 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.]

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) [Time Frame: 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.]

Number of Participants With Abnormalities in Electrocardiograms [Time Frame: 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.]

Number of Participants With Abnormalities in Vital Signs [Time Frame: 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.]

Number of Participants With Best Overall Response [Time Frame: at 6 months]

Number of Participants With Grade 1-4 Hematology Abnormalities (as Per the NCI CTCAE, Version 3.0) [Time Frame: 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.]

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) [Time Frame: 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.]

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) [Time Frame: 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.]

Participants With Freedom-From-Progression (FFP) at 6 Months [Time Frame: at 6 months]

Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months [Time Frame: at 6 months]

Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms [Time Frame: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)]

Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms [Time Frame: 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]

Secondary ID(s)

CA180-261

Source(s) of Monetary Support

Please refer to primary and secondary sponsors