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

This study has been terminated.
(This study has closed to accrual early due to slow accrual.)
Sponsor:
Collaborators:
Brigham and Women's Hospital
Bayer
Breast Cancer Research Foundation
Information provided by (Responsible Party):
Nancy Lin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00496379
First received: July 3, 2007
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
CNS Disease
Drug: ZK219477
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ZK219477 (ZK-EPO) in Patients With Breast Cancer and Brain Metastases

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Objective Response Rate in the Central Nervous System (CNS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Subjects With Adverse Events (Any Grade) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Adverse events per NCI CTCAE

  • Objective Response Rate in Non-Central Nervous System (CNS) Sites [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Non-CNS response rate (according to RECIST 1.0) limited to patients with measurable non-CNS disease

  • Time to Progression at Any Site. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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

  • Clinical Benefit Rate. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    CBR = CR + PR + SD > 24 weeks in CNS with at least stable non-CNS disease


Enrollment: 15
Study Start Date: July 2007
Study Completion Date: January 2012
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ZK219477 Drug: ZK219477
Given intravenously over approximately 30 minutes once every 3 weeks
Other Names:
  • ZK-EPO
  • ZK-Epothilone
  • Sagopilone

Detailed Description:
  • 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00496379

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Nancy Lin, MD
Brigham and Women's Hospital
Bayer
Breast Cancer Research Foundation
Investigators
Principal Investigator: Nancy Lin, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Nancy Lin, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00496379     History of Changes
Other Study ID Numbers: 06-268
Study First Received: July 3, 2007
Results First Received: November 30, 2012
Last Updated: March 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
metastatic breast cancer
invasive breast cancer
brain metastases
ZK-EPO

Additional relevant MeSH terms:
Neoplasm Metastasis
Breast Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 18, 2014