Randomized Trial of Fulvestrant With or Without Dasatinib in Men and Postmenopausal Women Who Have Hormone Receptor-positive Advanced Breast Cancer Previously Treated With an Aromatase Inhibitor

Study Overview
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Brief Summary
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The purpose of this study is to find out what effect the combination of fulvestrant (Faslodex) and dasatinib (Sprycel) has on advanced breast cancer compared to fulvestrant alone.

Official Title
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Phase II Randomized Trial of Fulvestrant With or Without Dasatinib in Men and Postmenopausal Women Who Have Hormone Receptor-positive Advanced Breast Cancer Previously Treated With an Aromatase Inhibitor

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Dasatinib
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb (BMS) clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Histologically confirmed hormone receptor positive (HR+) [(estrogen receptor (ER+) and/or progesterone receptors(PgR+)] breast cancer according to immunohistochemistry (IHC) Measureable or evaluable-only disease human epidermal growth factor receptor 2+ (HER2+) or HER2- breast cancer Males and females ≥18 years of age Females are post menopausal or surgically sterile Recurrent or progressive advanced breast cancer (locally-advanced or metastatic), that has progressed: (a) during or within 12 months after completion of adjuvant Aromatase Inhibitor (AI) treatment OR (b) during AI treatment in advanced setting (metastatic therapy) Exclusion Criteria: Pregnant or breast feeding >1 chemotherapy regimen for advanced disease Pleural or pericardial effusion Serious cardiac condition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 (Dasatinib +Fulvestrant)<br> | Drug: Dasatinib<br>* Tablets, Oral, 100 mg, once daily (QD), upto 2 years<br>* Other names: Sprycel;Drug: Fulvestrant<br>* Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1. In subsequent cycles, 500 mg IM administered on Day 1. IM day 1 and 15 first cycle then IM Day 1 for all other cycles for 2 years<br>* Other names: Faslodex;|
| Active Comparator: Arm 2 (Fulvestrant)<br> | Drug: Fulvestrant<br>* Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1. In subsequent cycles, 500 mg IM administered on Day 1. IM day 1 and 15 first cycle then IM Day 1 for all other cycles for 2 years<br>* Other names: Faslodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease Progression (PD) or Death | This endpoint evaluated the progression free survival (PFS) of participants amongst the total evaluable population. Progression free survival (PFS) was defined as the time from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Participants with no recorded post-baseline tumor assessment had PFS censored at the day of randomization. Participants lost to follow-up were censored at the last date of contact. Participants that had not progressed or died had PFS censored at the date of last follow-up. | Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time of Progression-free Survival (PFS) | Progression free survival (PFS) was defined as the time in months from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years) | 
| Percentage of Participants With Progression Free Survival (PFS) at 6 Months | PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 6 months after randomization. Progression free survival (PFS) was defined as the time from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Kaplan Meier assessments were used to estimate the percentages. | at 6 months | 
| Percentage of Participants With Clinical Benefit for At Least 6 Months | Clinical benefit rate (CBR) was defined as the percentage of participants that had Stable Disease (SD), complete response (CR), or partial response (PR) for greater than or equal to 6 months if there was no evidence of progression at or before assessment performed on or after Study Day 161. CR= Disappearance of all target lesions. No new lesions. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Physical examination, radiological assessment, and bone scans (if applicable) were used to assess outcome. | Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years) | 
| Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD) | Table represents the best response achieved over this time frame. CR = Disappearance of all target lesions. No new lesions. PR = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years) | 
| Number of Participants With Best Overall Response | Best overall response rate (ORR) = number of participants with measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) having a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. RECIST 1.1 response criteria applies. To be recorded as best response, CR or PR had to be confirmed at ≥ 4 weeks interval. An unconfirmed CR was recorded as PR. | Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years) | 
| Number of Participants With Serious Adverse Events, Death, and Discontinuation Due to Adverse Events | Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. | Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years) |