Clinical Trial of Intravenous Alvespimycin in Patients With Her2 Positive Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the anti-tumor activity (via objective response rate) of alvespimycin in patients with breast cancer who have not previously received trastuzumab (except as adjuvant therapy).

Official Title
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Phase 2 Clinical Trial of Intravenous Alvespimycin [KOS-1022] in Patients With Her2 Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Alvespimycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: KPS performance status of >= 80% (normal activity with effort) Metastatic breast cancer with Her2 amplification by FISH or 3+ Her2 overexpression by immunohistochemistry (IHC) Must have received no more than one prior cytotoxic chemotherapy regimen in the metastatic setting Measurable disease by RECIST Criteria Exclusion Criteria: Received prior lapatinib, an investigational ErbB-2 and/or an investigational EGFR dual tyrosine kinase inhibitors Administration of any other chemotherapy, biological, immunotherapy or investigational agent within 14 days prior to receipt of study medication Pregnant or breast-feeding women. Known CNS metastases, unless treated and without clinically significant neurological deficits Moderately severe dry eye Congestive heart failure, or a left ventricular ejection fraction Myocardial infarction or active ischemic heart disease within 12 months prior to study drug administration Previous malignancies unless free of recurrence for at least 5 years

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: A1<br> | Drug: Alvespimycin<br>* Solution, IV, Alvespimycin 80 mg/m2, Weekly one hour infusion Days 1, 8, and 15, every 4 weeks thereafter until disease progression or DLT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate (either RECIST or WHO complete response, partial response or minor response) confirmed by CT and MRI as the preferred methods for tumor assessments and Chest x-ray is acceptable for pulmonary lesions | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events assessed according to the NCI CTCAE (v 3.0) grading system | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment, and for 167 days | 
| Laboratory tests assessed according to the NCI CTCAE (v 3.0) grading system |  | Within 10 days prior to Cycle 1/1st infusion; within 48 hours of infusion (Cycle 1/Weeks 2/3/4 and Cycle 2+/Week3), or within 72 hours prior to infusion (Cycle 2+/Week 1) | 
| Vital signs | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment, Day1 of Weeks 1, 2, and 3 of Cycle 1 (4 weeks long), and prior to each 4-week cycle starting with Cycle 2, for 167 days | 
| Karnofsky Performance Status | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment, prior to each 4-week cycle starting with Cycle 2, for 167 days | 
| Ocular testing | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment, Cycle 1/Day 10 (3 days +/- 1 day following the 2nd infusion in the first cycle of therapy), prior to Cycle 2, if clinically indicated thereafter, for 167 days | 
| Kaplan-Meier estimate of time to progression | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Time to progression on the patient's prior cytotoxic chemotherapy compared to the patient's time to progression on alvespimycin | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Kaplan-Meier estimate of progression-free survival | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Kaplan-Meier estimate of time to response | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Kaplan-Meier estimate of duration of response | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Kaplan-Meier estimate of time to treatment failure | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Kaplan-Meier estimate of overall survival | (all patients were off study by June 2008) | Within 28 days prior to the start of treatment with tumor assessments reevaluated every 8 weeks (+/- 4 days) | 
| Changes in tumor markers |  | Within 28 days prior to the start of treatment, Prior to each 4-week cycle starting with Cycle 2, for 167 days | 
| Histopathological and molecular profile of responding and non-responding patients using paraffin-embedded surgical specimens |  | Specimens were obtained within 28 days prior to the start of treatment |