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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: BMS-754807; Drug: letrozole

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ Of Al At Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology Research
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois Cancercare, Pc
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Indiana University Health Goshen Center for Cancer Care
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21231-1000
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Wheaton, Maryland, United States, 20902
      • Oncology Care Associates, P.A.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Ctr, University Of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Unv. Of Nc At Chapel Hill
    • Chapel Hill, North Carolina, United States, 27599-7305
      • Unv. Of Nc At Chapel Hill
    • Charlotte, North Carolina, United States, 28204
      • Presbyterian Hospital Cancer Research
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center-Dept Of Medicine
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Ut Md Anderson Can Ctr.
    • Houston, Texas, United States, 77030
      • Ut Md Anderson Can Ctr.
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BMS-754807	Drug: BMS-754807; Tablet, Oral, 100 mg, Daily, Until disease progression or unacceptable toxicity
EXPERIMENTAL: BMS-754807 + letrozole	Drug: BMS-754807; Tablet, Oral, 100 mg, Daily, Until disease progression or unacceptable toxicity; Drug: letrozole; Tablets, Oral, 2.5 mg, Daily, Until disease progression or unacceptable toxicity; Other Names: Femara®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Mayo Clinic

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 31, 2010
• Primary Completion (ACTUAL): November 30, 2014
• Study Completion (ACTUAL): November 30, 2014

Study Registration Dates

• First Submitted: October 19, 2010
• First Submitted That Met QC Criteria: October 19, 2010
• First Posted (ESTIMATE): October 20, 2010

Study Record Updates

• Last Update Posted (ACTUAL): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: CA191-011