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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Dasatinib; Drug: Letrozole

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Sedona, Arizona, United States, 86336
      • Northern Arizona Hematology & Oncology Associates
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates D.B.A. Hematology Oncology
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers
  • Florida
    • Hudson, Florida, United States, 34667
      • Florida Cancer Institute - New Hope
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Central Indiana Cancer Centers
  • New York
    • Troy, New York, United States, 12180
      • New York Oncology Hematology, PC
  • Ohio
    • Kettering, Ohio, United States, 45409
      • Dayton Oncology And Hematology
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Center
    • Portland, Oregon, United States, 97213
      • Northwest Cancer Specialists, PC
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Medical Oncology Associates
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology-Central Austin Cancer Center
    • Bedord, Texas, United States, 76022
      • Texas Oncology
    • Dallas, Texas, United States, 75230
      • Texas Cancer Center at Medical City
    • Dallas, Texas, United States, 75231
      • Texas Oncology
    • Dallas, Texas, United States, 75246
      • Texas Oncology Sammons Cancer Center
    • El Paso, Texas, United States, 79915
      • El Paso Cancer Treatment Ctr - East
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology
    • Garland, Texas, United States, 75042
      • Texas Oncology
    • Houston, Texas, United States, 77024
      • Texas Oncology
    • Plano, Texas, United States, 75075
      • Texas Oncology-Plano East
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology Cancer Center - Sugar Land
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
    • Waco, Texas, United States, 76712
      • Texas Oncology Cancer Care and Research Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Salem, Virginia, United States, 24153
      • Oncology & Hematology Associates of Southwest Virginia, Inc.
  • Washington
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/North Star Lodge

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A1	Drug: Dasatinib; Tablets, Oral, 100 mg once daily, up to 2 years; Other Names: BMS-354825; Sprycel; Drug: Letrozole; Tablets, Oral, 2.5 mg, once daily, up to 2 years; Other Names: Femara
Active Comparator: A2	Drug: Letrozole; Tablets, Oral, 2.5 mg, once daily, up to 2 years; Other Names: Femara

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: US Oncology Research

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: June 10, 2008
• First Submitted That Met QC Criteria: June 10, 2008
• First Posted (Estimate): June 12, 2008

Study Record Updates

• Last Update Posted (Estimate): June 13, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

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; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Dasatinib
• Other Study ID Numbers: CA180-185; USOR 06-185