Study of BMS-754807 Combined With Letrozole or BMS-754807 Alone in Patients With Hormone Receptor-Positive Breast Cancer and Resistance to Non-Steroidal Aromatase Inhibitors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate oral doses of BMS-754807 in combination with letrozole or BMS-754807 alone are safe and efficacious in locally advanced or metastatic hormone receptor positive breast cancer subjects who have progressed with prior non-steroidal aromatase inhibitor treatment.

Official Title
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A Phase 2 Study of BMS-754807 Combined With Letrozole or BMS-754807 Alone in Hormone Receptor-Positive Breast Cancer Subjects With Acquired Resistance to Non-Steroidal Aromatase Inhibitors

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: BMS-754807
* 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: Postmenopausal women with hormone receptor-positive and HER-2 negative breast cancer Disease progression following non-steroidal aromatase inhibitor treatment Exclusion Criteria: Known symptomatic brain metastasis Medical condition requiring chronic steroids History of Type 1 or 2 Diabetes Uncontrolled or significant cardiovascular (CV) disease Concomitant second malignancies

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 |
| --- | --- |
| Experimental: BMS-754807<br> | Drug: BMS-754807<br>* Tablet, Oral, 100 mg, Daily, Until disease progression or unacceptable toxicity<br>|
| Experimental: BMS-754807 + letrozole<br> | Drug: BMS-754807<br>* Tablet, Oral, 100 mg, Daily, Until disease progression or unacceptable toxicity<br>Drug: letrozole<br>* Tablets, Oral, 2.5 mg, Daily, Until disease progression or unacceptable toxicity<br>* Other names: Femara®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Rate at 24 Weeks | Progression free survival (PFS) rate at 24 weeks after treatment with BMS 754807/letrozole was to be calculated as the total number of subjects neither progressed nor died after 24 weeks of treatment divided by the total number of subjects (with measurable or non-measurable disease) randomized/assigned to combination treatment arm and treated. In participants with measurable disease Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) criteria was to be used to assess disease progression.This outcome was not measured due to early termination of the study. | 24 weeks after initiation of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Objective Response Rate (ORR) in Participants With Measurable Disease | ORR is defined as the number of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) divided by the number of participants who received treatment. Participants were to be evaluated for tumor response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions.: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. This outcome measure was not met due to early termination of the study | 24 weeks after initiation of study treatment | 
| Number of Participants With Adverse Events (AEs), Serious AEs, Non-serious AEs , Discontinuation Due to AEs and Deaths | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. | Non-SAEs: Day 1 to 7 days after the participant discontinues study medication or 7 days after the End of Treatment visit (up to 42 months), For SAEs: during the screening period and within 30 days of discontinuation of dosing ,up to 42 months | 
| Duration of Response (DOR) in Participants With Measurable Disease | DOR was to be performed to further characterize the response rate at Week 24. Duration of response is defined as the time between the Week 25 date of response and the date of objectively documented disease progression as defined by modified RECIST 1.1 criteria or death, whichever occurs first. DOR could not be assessed due to early termination of the study. | 24 weeks after initiation of study treatment | 
| Number of On-study Laboratory Abnormalities: Grade 1-2 | Blood and urine samples were obtained at specified times points for laboratory evaluations. Clinical Laboratory Sage Panels included: Hematology: Hemoglobin, Hematocrit, Red blood cell, Total leukocyte count, including differential, Platelet count. Serum Chemistry : Albumin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALK-P), Bilirubin, total (TB). Reflex testing of direct (conjugated) and indirect (unconjugated) bilirubin will be ordered if total bilirubin > 5X ULN, Blood urea nitrogen (BUN or urea), Calcium, Chloride, Cholesterol, Creatinine, serum, Glucose, fasting plasma, Lactate dehydrogenase (LDH), Magnesium, Phosphorus, Potassium, Protein, total, Sodium, Triglycerides, Uric acid Urinalysis, Blood, Glucose, Ketones, Leukocyte esterase, pH, Protein. Laboratory tests were graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0 criteria | Assessed from day 1 up to within 30 days of last dose (Approximately 42 months) | 
| Number of On-study Laboratory Abnormalities: Grade 3-4 | Blood and urine samples were obtained at specified times points for laboratory evaluations. Clinical Laboratory Sage Panels included: Hematology: Hemoglobin, Hematocrit, Red blood cell, Total leukocyte count, including differential, Platelet count. Serum Chemistry : Albumin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALK-P), Bilirubin, total (TB). Reflex testing of direct (conjugated) and indirect (unconjugated) bilirubin will be ordered if total bilirubin > 5X ULN, Blood urea nitrogen (BUN or urea), Calcium, Chloride, Cholesterol, Creatinine, serum, Glucose, fasting plasma, Lactate dehydrogenase (LDH), Magnesium, Phosphorus, Potassium, Protein, total, Sodium, Triglycerides, Uric acid Urinalysis, Blood, Glucose, Ketones, Leukocyte esterase, pH, Protein Laboratory tests were graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0 criteria | Assessed from day 1 up to within 30 days of last dose (Approximately 42 months) | 
| Treatment Failure Rate (TFR) | The TFR was to be calculated as the total number of subjects who discontinued the treatment for any reason (including disease progression, treatment toxicity, and death) at 24 weeks divided by the total number of subjects randomized/assigned to the arm and treated. In the monotherapy arm, the TFR was to be assessed while subjects were on monotherapy. | 24 weeks after initiation of study treatment | 
| Changes in Absolute Copy Numbers and Relative Expression of Insulin Receptor Isoform A (IR-A) in Tumor Tissue in Response to Treatment | Absolute copy numbers and relative expression of insulin receptor isoforms (IR-A, IR-B) in pre- and posttreatment fresh tumor tissues were to be measured. This outcome was not measured due to early termination of the study. | 24 weeks after initiation of study |