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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01225172
• Other study ID #: CA191-011
• Status: Terminated
• Phase: Phase 2
• Start date: December 31, 2010
• Est. completion date: November 30, 2014

Study information

• Verified date: August 2020
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: November 30, 2014
• Est. primary completion date: November 30, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• BMS-754807
Tablet, Oral, 100 mg, Daily, Until disease progression or unacceptable toxicity
• letrozole
Tablets, Oral, 2.5 mg, Daily, Until disease progression or unacceptable toxicity

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins	Baltimore	Maryland
United States	Univ Of Al At Birmingham	Birmingham	Alabama
United States	Unv. Of Nc At Chapel Hill	Chapel Hill	North Carolina
United States	Unv. Of Nc At Chapel Hill	Chapel Hill	North Carolina
United States	Presbyterian Hospital Cancer Research	Charlotte	North Carolina
United States	University Of Virginia Health System	Charlottesville	Virginia
United States	University Of Chicago Medical Center	Chicago	Illinois
United States	Duke University Medical Center-Dept Of Medicine	Durham	North Carolina
United States	Indiana University Health Goshen Center For Cancer Care	Goshen	Indiana
United States	Ut Md Anderson Can Ctr.	Houston	Texas
United States	Ut Md Anderson Can Ctr.	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	University Of Wisconsin	Madison	Wisconsin
United States	University Of Wisconsin	Madison	Wisconsin
United States	Masonic Cancer Ctr, University Of Minnesota	Minneapolis	Minnesota
United States	Illinois Cancercare, Pc	Peoria	Illinois
United States	Mayo Clinic	Rochester	Minnesota
United States	Sharp Clinical Oncology Research	San Diego	California
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Oncology Care Associates, P.A.	Wheaton	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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

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