A Study of Epothilone D in Combination With Herceptin (Trastuzumab) in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This single arm study will determine the efficacy and safety of an epothilone D and Herceptin combination regimen in patients with HER-2 positive locally advanced or metastatic breast cancer. Epothilone D will be administered intravenously on days 1, 8 and 15 every 4 weeks at a dose not exceeding 100mg/m2. Herceptin will be administered intravenously on a weekly schedule; a 4mg/kg loading dose will be followed by a weekly maintenance dose of 2mg/kg. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.

Official Title
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An Open-label Study to Evaluate the Effect of Combination Therapy With Epothilone D and Herceptin on Tumor Response in Patients With HER-2 Overexpressing Locally Advanced or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Epothilone D
* Drug: Herceptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women >=18 years; locally advanced or metastatic breast cancer; HER-2 overexpression (FISH + or IHC 3+); >=1 measurable lesion; up to one prior anthracycline-based chemotherapy regimen in a metastatic setting. Exclusion Criteria: pre-existing neuropathy >=grade 2; known CNS metastases; congestive heart failure, or myocardial infarction within the last 6 months; previous malignancies in last 5 years, except for cured basal cell cancer of the skin, or cancer in situ of the cervix.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I - Epothilone D Dose Escalation<br> | Drug: Epothilone D<br>* ≤100 mg/m^2 intravenously (iv) on days 1, 8 and 15 once every 4 weeks<br>* Other names: KOS-862;Drug: Herceptin<br>* 4mg/kg iv loading dose, followed by 2mg/kg iv weekly<br>* Other names: Trastuzumab;|
| Experimental: Phase II - Epothilone D Maximum Tolerated Dose<br> | Drug: Epothilone D<br>* ≤100 mg/m^2 intravenously (iv) on days 1, 8 and 15 once every 4 weeks<br>* Other names: KOS-862;Drug: Herceptin<br>* 4mg/kg iv loading dose, followed by 2mg/kg iv weekly<br>* Other names: Trastuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Number of Participants with a Dose-Limiting Toxicity |  | From first dose of study treatment until end of Cycle 1 (1 cycle is 28 days) | 
| Phase II: Objective Response Rate (per RECIST criteria) |  | From first dose of study treatment until documented response (up to 3 years, 2 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Duration of Response |  | From date of objective response until progressive disease or death, whichever occurs first (up to 3 years, 2 months) | 
| Phase II: Time to Tumor Progression |  | From first dose of study treatment until progressive disease or death, whichever occurs first (up to 3 years, 2 months) | 
| Phase I: Plasma Concentration of Epothilone D at Specified Timepoints |  | Cycle 1 Days -2, -1, and 1; Cycle 2 Days 1 15-17 (1 cycle is 28 days) | 
| Number of Participants with at Least One Adverse Event |  | From first dose of study treatment until 28 days after last dose (up to 3 years, 2 months) |