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

• ClinicalTrials.gov Identifier: NCT00496379
• Recruitment Status: Terminated
• First Posted: July 4, 2007
• Results First Posted: March 12, 2013
• Last Update Posted: March 14, 2013
• Sponsor: Nancy Lin, MD
• Collaborators: Brigham and Women's Hospital; Bayer; Breast Cancer Research Foundation
• Information provided by (Responsible Party): Nancy Lin, MD, Dana-Farber Cancer Institute

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Cancer; CNS Disease	Drug: ZK219477	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of ZK219477 (ZK-EPO) in Patients With Breast Cancer and Brain Metastases
• Study Start Date: July 2007
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: January 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: ZK219477	Drug: ZK219477; Given intravenously over approximately 30 minutes once every 3 weeks; Other Names: ZK-EPO; ZK-Epothilone; Sagopilone

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate in the Central Nervous System (CNS) [ Time Frame: 2 years ]
   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 :

1. Number of Subjects With Adverse Events (Any Grade) [ Time Frame: 2 years ]
   Adverse events per NCI CTCAE
2. Objective Response Rate in Non-Central Nervous System (CNS) Sites [ Time Frame: 2 years ]
   Non-CNS response rate (according to RECIST 1.0) limited to patients with measurable non-CNS disease
3. Time to Progression at Any Site. [ Time Frame: 2 years ]
   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
4. Clinical Benefit Rate. [ Time Frame: 2 years ]
   CBR = CR + PR + SD > 24 weeks in CNS with at least stable non-CNS disease

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes 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

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

• Responsible Party: Nancy Lin, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00496379
• Other Study ID Numbers: 06-268
• First Posted: July 4, 2007
• Results First Posted: March 12, 2013
• Last Update Posted: March 14, 2013
• Last Verified: March 2013

Keywords provided by Nancy Lin, MD, Dana-Farber Cancer Institute:

metastatic breast cancer; invasive breast cancer; brain metastases; ZK-EPO

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Central Nervous System Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Neoplastic Processes; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Nervous System Diseases; Epothilones; Sagopilone; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents