Randomized Phase II Trial of Letrozole With or Without Dasatinib as First and Second-line Treatment for Hormone Receptor-positive, HER2-negative Post-menopausal Breast Cancer That is Unresectable, Locally Recurrent or Metastatic

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 letrozole (brand name: Femara) and dasatinib (brand name: Sprycel) has on metastatic breast cancer compared to letrozole alone

Official Title
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Randomized Phase II Trial of Letrozole With or Without Dasatinib as First and Second-line Treatment for Hormone Receptor-positive, HER2-negative Post-menopausal Breast Cancer That is Unresectable, Locally Recurrent or Metastatic

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Dasatinib
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Has histologic or cytologic diagnosis of breast cancer; evidence of unresectable locally recurrent or metastatic disease Has measurable or evaluable-only disease Is female, ≥18 yrs of age, post menopausal or surgically sterile HER2 negative, HR+, ER+ and/or PgR+ breast cancer 0-1 prior chemotherapy regimen for metastatic disease. Prior adjuvant or neoadjuvant chemotherapy completed at least 1 month prior Prior tamoxifen therapy is allowed No AI therapy for >1 year without recurrence Exclusion Criteria: Pregnant or breast feeding Prior hormonal therapy for metastatic or locally recurrent disease >1 chemotherapy regimen for metastatic 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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Female

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: A1<br> | Drug: Dasatinib<br>* Tablets, Oral, 100 mg once daily, up to 2 years<br>* Other names: BMS-354825;Drug: Letrozole<br>* Tablets, Oral, 2.5 mg, once daily, up to 2 years<br>* Other names: Femara;|
| Active Comparator: A2<br> | Drug: Letrozole<br>* Tablets, Oral, 2.5 mg, once daily, up to 2 years<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Benefit (CBR) and Number of Participants With CBR Having a Disease Free Interval (DFI) Greater Than 2 Years - Evaluable Population | CBR=participants with complete response (CR) + participants with partial response (PR) + participants with stable disease (SD) for a length of time greater than, equal to 6 months. 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. | First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Response, Partial Response, Stable Disease, and Disease Progression | 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. | First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years) | 
| Median Progression Free Survival (PFS) - Intent to Treat (ITT) Population | PFS was measured in months. 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. Study initiated 2008 and completed 2014. | Day 1 to Study Completion (approximately 6 years) | 
| Percentage of Participants Best Overall Response After Change From Letrozole to Letrozole Plus Dasatinib | Participants in single-agent letrozole treatment arm who developed progressive disease, could continue letrozole, and add dasatinib to their treatment regimen. CBR=participants with CR + participants with partial response (PR) + participants with SD for a length of time ≥6 months divided by the total number of participants (%). 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. 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. | First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years) | 
| Percentage of Participants With PFS At 6 Months and At 12 Months - ITT Population | 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. ITT population: from time of first enrollment to first PD for all ITT participants. | At 6 months and at 12 months | 
| Median Time to Treatment Failure (TTF) - ITT Population | Time to TTF was measured in months. The number of participants with events (PD or off treatment due to any reason) was evaluated. The first PD was defined as the event for cross over participants in the single- agent letrozole treatment arm to add dasatinib to their regimen. | First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years) | 
| Number of Participants With Adverse Events (AEs) Leading to Discontinuation, Serious Adverse Events (SAEs), and Deaths | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=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. | First dose of study drug to last dose plus 30 days, up to study completion (approximately 6 years) |