Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer

NCT00767520 | Completed Phase 2 Results DMC

• 1 other identifier: CA180-261
• Study Type: interventional
• Target: 155
• Locations: 8 countries
• Sites: 21

Brief Summary

The purpose of this study is to determine whether exemestane plus dasatinib will be well-tolerated and will increase progression-free survival (PFS) in the treatment of advanced estrogen-receptor positive (ER+) breast cancer after disease progression (PD) on a non-steroidal aromatase inhibitor (NSAI).

Conditions

Breast Cancer

Keywords

Advanced Estrogen Receptor Positive Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo

  PFS= The time (weeks) from date of randomization to date of progressive disease(PD). PFS for each randomization arm was estimated using the Kaplan-Meier product-limit method. A point estimate and a 95% confidence interval (CI) for the median PFS was computed for each randomization arm using the Brookmeyer \& Crowley method. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).

  Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)

• Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo

  PD is an increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).

  Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)

Secondary Outcomes (14)

• Number of Participants With Best Overall Response

  at 6 months

• Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months

  at 6 months

• Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms

  Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)

• Participants With Freedom-From-Progression (FFP) at 6 Months

  at 6 months

• Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms

  Prior to study therapy, at 8 week intervals until CR or PR. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer

Study Arms (2)

A

ACTIVE COMPARATOR

Drug: Exemestane + Dasatinib

B

PLACEBO COMPARATOR

Drug: Exemestane + Placebo

Interventions

Exemestane + Dasatinib DRUG

Tablets, Oral, Exemestane 25 mg + Dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity

Also known as: Sprycel, BMS-354825

A

Exemestane + Placebo DRUG

Tablets, Oral, Exemestane 25 mg + Placebo 100 mg, once daily, until disease progression or unacceptable toxicity

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-documented invasive estrogen receptor positive breast cancer , with tumor tissue from prior surgery available for analysis
• Prior therapy with a non-steroidal aromatase inhibitor
• Recurrent or progressive advanced breast cancer (locally-advanced or metastatic)
• Documented breast cancer with tumor ≤ 28 days prior to study entry
• Women who are NOT of childbearing potential
• Must be able to take oral medication
• Performance Status 0 or 1

You may not qualify if:

• Pleural or pericardial effusion or ascites (of any etiology; Grade ≥ 1) within 6 months prior to study entry
• Any chemotherapy, immunotherapy \< 6 months before study entry. Any targeted therapy (eg. lapatinib) \< 6 months before study entry, unless given in combination with an NSAI
• Any antitumor therapy, including radiotherapy or hormonal therapy, within 15 days prior to study entry
• Prior exposure to exemestane, any Src-family kinase inhibitor including dasatinib, to agents intended to control osteolytic disease other than bisphosphonates, or to any investigational agent for breast cancer
• Concurrent or previous malignant disease requiring chemotherapy or radiation treatment within the prior 3 years
• Significant bleeding disorder, or ongoing or recent clinically-significant gastrointestinal bleeding
• Any serious cardiac condition, including congestive heart failure or myocardial infarction within 6 months, uncontrolled angina, or Class III or IV heart disease as defined by the New York Heart Association, baseline ejection fraction ≤ 40%, diagnosed congenital long QT syndrome, clinically-significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes), QTc interval \> 450 msec at baseline (Fridericia correction)
• Hematologic abnormality Grade ≥ 2
• Hypocalcemia of Grade ≥ 1
• Any Chemistry abnormality of Grade ≥ 2 \[except Grade 2 indirect bilirubin permitted if diagnosed Gilbert's disease\]
• Pregnant Women and Women of Childbearing Potential (WOCBP)
• Extremely lactose intolerant, in the judgment of treating physician (100 mg dasatinib contains 135 mg lactose, posing a problem only if intolerance is severe)
• Receiving any of the following concomitant medications: Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Subjects must discontinue drug use at least 7 days prior to starting dasatinib)
• Potent inhibitors of CYP3A4 isoenzyme
• Prisoners or subjects who are involuntarily incarcerated; or subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (21)

Compassionate Cancer Care Medical Group, Inc

Fountain Valley, California, 92708, United States

Location

Compassionate Cancer Care Medical Group Inc

Riverside, California, 92501, United States

Location

Pennsylvania Oncology/Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Local Institution

Hradec Králové, 500 05, Czechia

Location

Local Institution

Prague, 150 06, Czechia

Location

Local Institution

Lille, 59000, France

Location

Local Institution

Paris, 75651, France

Location

Local Institution

Saint-Cloud, 92211, France

Location

Local Institution

Dublin, Dublin, 24, Ireland

Location

Local Institution

Gdansk, 80-462, Poland

Location

Local Institution

Gdansk, 80-952, Poland

Location

Local Institution

Lodz, 93-509, Poland

Location

Local Institution

Opole, 45-060, Poland

Location

Local Institution

Madrid, 28033, Spain

Location

Local Institution

Madrid, 28041, Spain

Location

Local Institution

Torrevieja, 03186, Spain

Location

Local Institution

Västerås, 72189, Sweden

Location

Local Institution

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Local Institution

London, Greater London, NW1 2BU, United Kingdom

Location

Local Institution

Coventry, Warwickshire, CV22DX, United Kingdom

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Breast Neoplasms

Interventions

exemestane; Dasatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: October 7, 2008
• Study Start: February 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: December 1, 2012
• Last Updated: February 28, 2013
• Results First Posted: June 11, 2012

Record last verified: 2012-07

Locations

CZ (2); GB (3); IE (1); PL (4); US (4); ES (3); FR (3); SE (1)