Breast Cancer
Conditions
Keywords
Advanced or Metastatic Her-2-positive Breast Cancer
Brief 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
Interventions
DRUGBMS-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
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
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| Assess anti-tumor activity of combination at MTD of BMS-754807 (dose expansion cohort) | Every 8 weeks |
| Evaluate safety and tolerability of the combination regimen | Ongoing |
| Assess effect of combination therapy on glucose metabolism | At 30 days, then every 8 weeks |
| Explore whether co-medication with oral anti-hyperglycemic agent can enable adequate tolerability of the combination therapy if BMS-754807 induces hyperglycemia | Ongoing |
| Obtain BMS-754807 plasma concentrations vs time data for future population PK analysis | Days, 1,8,15,22 |
Countries
Australia, Belgium, Canada, Hungary, United Kingdom
Outcome results
None listed