ZK219477 (Sagopilone) in Patients With Breast Cancer and Brain Metastases

Study Overview
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Brief Summary
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The purpose of this research study is to determine the effects (good and bad) of ZK219477(sagopilone) on participants and their cancer. ZK219477 is a chemotherapy drug that is thought to work by interfering with the ability of cancer cells to grow and divide. It is a part of a group of drugs called epothilones which appear to cause shrinkage of cancer in some patients with breast cancer. It is generally difficult for chemotherapy to enter the brain. However, it is believed that ZK219477 crosses into the brain. We are also studying whether an investigational MRI scan procedure may eventually help to predict which patients will benefit from ZK219477.

Detailed Description
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Participants will be given ZK219477 intravenously over approximately 30 minutes every three weeks. During all treatment cycles a physical exam and questions about the participants general health and specific questions about any problems they may be having will be performed. At least every three weeks blood tests will be done to assess the effect of ZK219477 on the body. After every 2 cycles of treatment, participants will have additional scans to assess the effect of ZK219477 on their cancer. This will include a CT scan of the abdomen, chest, and pelvis, and an MRI of the brain. At the time of the standard MRI, participants will be asked to undergo an additional MRI sequence, which means they will be in the MRI machine for approximately 15-20 more minutes.

Official Title
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A Phase 2 Study of ZK219477 (ZK-EPO) in Patients With Breast Cancer and Brain Metastases

Conditions
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Breast Cancer, CNS Disease

Intervention / Treatment
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* Drug: ZK219477


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically invasive breast cancer, with metastatic disease at the time of screening Measurable Central Nervous System (CNS) disease, as defined as at least one lesion > or equal too 10mm in longest dimension New or progressive CNS lesions after at least one prior standard CNS-directed therapy for treatment of brain metastases, which could include surgical resection, whole brain radiotherapy (WBRT), and/or stereotactic radiosurgery (SRS). Patients must have received prior WBRT, SRS or both. Patient has been evaluated by a radiation oncologist, who feels that the plan to evaluate systemic chemotherapy in place of additional brain radiotherapy is an acceptable option No increase in corticosteroid use in the week prior to study entry Any number prior lines of chemotherapy for metastatic breast cancer 18 years of age of older Life expectancy of greater than 12 weeks ECOG Performance Status 0-2 Patients must have normal organ function as outlined in the protocol Exclusion Criteria: Patients who have had chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier Patients who have had XRT within 3 weeks prior to entering the study or those who have not recovered from adverse events due to XRT Patients may not be receiving any other investigational agent Patients may not be receiving any cancer-directed therapy Prior treatment with investigational chemotherapy for brain metastases Prior treatment with epothilone for metastatic breast cancer Leptomeningeal carcinomatosis as the only site of CNS involvement. Concurrent treatment with an enzyme inducing antiepileptic drug, including phenytoin, carbamezepine, phenobarbital, or oxacarbazepine More than 2 seizures over the last four weeks prior to study entry Known contraindication to MRI or gadolinium contrast, such as cardiac pacemaker, ocular foreign body, or shrapnel Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or breastfeeding women.

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: ZK219477<br> | Drug: ZK219477<br>* Given intravenously over approximately 30 minutes once every 3 weeks<br>* Other names: Sagopilone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate in the Central Nervous System (CNS) | Objective response rate is defined as at least a 50 percent reduction in the Central Nervous system target lesion volume compared to the lesion volume at baseline. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Events (Any Grade) | Adverse events per NCI CTCAE | 2 years | 
| Objective Response Rate in Non-Central Nervous System (CNS) Sites | Non-CNS response rate (according to RECIST 1.0) limited to patients with measurable non-CNS disease | 2 years | 
| Time to Progression at Any Site. | Time from date of registration until the date of the first documentation of progression or date of death (from any cause),whichever came first, up to 2 years from registration. Progression is defined as either progression in the Central Nervous system (CNS) according to volumetric measurement (Freedman et al. 2011) and /or progression in non-Central Nervous System lesion Measured by RECIST 1.0 | 2 years | 
| Clinical Benefit Rate. | CBR = CR + PR + SD > 24 weeks in CNS with at least stable non-CNS disease | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ZK-EPO, metastatic breast cancer, invasive breast cancer, brain metastases