Combination Study of BMS-754807 and Herceptin® in Patients With Advanced or Metastatic Her-2-positive Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase I/II Trial of BMS-754807 in Combination With Trastuzumab (Herceptin®) in Subjects With Advanced or Metastatic Her-2-positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00788333
• Other study ID #: CA191-004
• Secondary ID: EUDRACT #: 2009-
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 7, 2008
• Last updated: July 12, 2012
• Start date: July 2009
• Est. completion date: November 2011

Study information

• Verified date: July 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Ministry of Health & Long Term Care, OntarioHungary: Ministry of HealthUnited Kingdom: National Institute for Health and Clinical Excellence
• Study type: Interventional

Clinical Trial Summary

This is a Phase I/II study to evaluate the safety profile, tolerability, pharmacokinetics and pharmacodynamics following daily oral doses of 50 to 200 mg of BMS-754807 in combination with trastuzumab (Herceptin®) in subjects with advanced or metastatic Her-2-positive breast cancer. In addition, the study is expected to identify the recommended dose or dose range of BMS-754807 in combination with trastuzumab for Phase II studies and provide preliminary evidence of anti-tumor activity in Her-2-positive breast cancer subjects after trastuzumab failure

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

For additional information on this trial, please call (910) 558-2913

Inclusion Criteria:

• Subjects with locally advanced or metastatic Her-2-positive breast cancer who have failed at least one trastuzumab containing regimen. Prior treatment with other Her-2-targeted agents (e.g. lapatinib, pertuzumab, trastuzumab DM-1 etc.) is allowed

• Histologic or cytologic diagnosis of Her-2-positive breast cancer

• ECOG status 0 - 1

Exclusion Criteria:

• Symptomatic brain metastasis

• Any condition requiring chronic use of steroids

• Any disorder with dysregulation of glucose homeostasis (history of Type 1 or 2 Diabetes Mellitus or prediabetic symptoms

• History of glucose intolerance

• Women of child-bearing potential unwilling or unable to use acceptable contraception methods

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• BMS-754807
Tablets, Oral, Dose escalation to MTD, then MTD to response/EOT, once daily, Varies - treatment is continued to disease progression or MD/subject/Sponsor decision to stop
• trastuzumab (Herceptin®)
IV solution, IV, 4mg/kg Day 1 loading dose, 2mg/kg once weekly, Varies - treatment is continued to disease progression or MD/subject/Sponsor decision to stop

Locations

Country	Name	City	State
Australia	Local Institution	Frankston	Victoria
Australia	Local Institution	Geelong	Victoria
Australia	Local Institution	Kurralta Park	South Australia
Belgium	Local Institution	Brussels
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Toronto	Ontario
Hungary	Local Institution	Budapest
Hungary	Local Institution	Miskolc
United Kingdom	Local Institution	Newcastle Upon Tyne	Tyne And Wear

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Hungary,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The dose escalation portion will determine the MTD and recommended Phase 2 dose or dose range of BMS-754807 when administered orally on a daily schedule in combination with trastuzumab administered at standard doses IV on a weekly basis		Every 30 days until MTD is reached	Yes
Secondary	Assess anti-tumor activity of combination at MTD of BMS-754807 (dose expansion cohort)		Every 8 weeks	Yes
Secondary	Evaluate safety and tolerability of the combination regimen		Ongoing	Yes
Secondary	Assess effect of combination therapy on glucose metabolism		At 30 days, then every 8 weeks	Yes
Secondary	Explore whether co-medication with oral anti-hyperglycemic agent can enable adequate tolerability of the combination therapy if BMS-754807 induces hyperglycemia		Ongoing	Yes
Secondary	Obtain BMS-754807 plasma concentrations vs time data for future population PK analysis		Days, 1,8,15,22	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form