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

Study Overview
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Brief Summary
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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

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: BMS-754807
* Drug: trastuzumab (Herceptin®)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Combination | Drug: BMS-754807<br>* 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<br>* Other names: IGF-IR;Drug: trastuzumab (Herceptin®)<br>* 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<br>* Other names: Herceptin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced or Metastatic Her-2-positive Breast Cancer