Epothilone B in Treating Patients With CNS Metastases From Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
David Peereboom, MD, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00450866
First received: March 20, 2007
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as epothilone B, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well epothilone B works in treating patients with CNS metastases from breast cancer.


Condition Intervention Phase
Breast Cancer
Metastatic Cancer
Biological: epothilone B
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Patupilone in Patients With Brain Metastases From Breast Cancer

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Central Nervous System (CNS) Progression-free Survival(PFS) [ Time Frame: 3 months after treatment ] [ Designated as safety issue: No ]

    The number of patients that are documented to have progression free survival at 3 months after treatment. Progression free is define as <25% increase in tumor area.

    PFS will be measured from the date of entry into the trial to the date of documented progression of brain metastases or death.



Secondary Outcome Measures:
  • Toxicity as Measured by NCI CTCAE v3.0 [ Time Frame: 3 months after treatment ] [ Designated as safety issue: Yes ]
    Percent of patients that experience the most common grade 3 and above toxicities possibly related to study drug - to be measured using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.

  • CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria [ Time Frame: 3 months after treatment ] [ Designated as safety issue: No ]
    Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of >50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a > 25% increase in tumor area (two diameters)

  • Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria [ Time Frame: 3 months after treatment ] [ Designated as safety issue: No ]
    Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of >50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a > 25% increase in tumor area (two diameters)

  • Overall Survival [ Time Frame: 48 months from start of study ] [ Designated as safety issue: No ]
    Median time (months) that patients survived during the duration of the study.


Enrollment: 55
Study Start Date: January 2007
Study Completion Date: May 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epothilone B Biological: epothilone B
Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.
Other Name: Patupilone

Detailed Description:

OBJECTIVES:

Primary

  • Determine the 3-month CNS-progression free survival of patients with CNS metastases secondary to breast cancer treated with epothilone B.

Secondary

  • Determine the toxicity of this drug in these patients.
  • Determine the CNS response rate and duration of CNS response in patients treated with this drug.
  • Determine the systemic disease response rate and duration of systemic response in patients treated with this drug.
  • Determine the overall survival of patients treated with this drug.

OUTLINE: This is a multicenter, open-label study.

Patients receive epothilone B IV over 20 minutes on day 1. Courses repeat every 21 days in the absence of disease progression, satisfactory response, or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed carcinoma of the breast
  • CNS metastases (i.e., brain parenchymal lesions and/or leptomeningeal disease), meeting 1 of the following criteria:

    • Recurrent or progressive CNS metastases after whole brain radiotherapy

      • If only evaluable site of CNS progression has been previously treated with stereotactic radiosurgery, radiation necrosis must be excluded by radiographic (e.g., positron emission tomography scan or magnetic resonance spectroscopy) or histologic assessment
    • Newly diagnosed, untreated, asymptomatic brain or leptomeningeal metastases
  • Patient must be neurologically stable, as demonstrated by a stable dose of steroids and anticonvulsants for ≥ 1 week prior to obtaining baseline gadolinium-enhanced MRI of the brain and/or ≥ 1 week prior to beginning study treatment
  • No CNS complications requiring urgent neurosurgical intervention (e.g., resection or shunt placement)
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Male or female
  • Menopausal status not specified
  • Karnofsky performance status 60-100%
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count > 1,500/mm^3
  • Hemoglobin > 9.0 g/dL
  • Platelet count > 100,000/mm^3 (red blood cell transfusion and repeat evaluation allowed)
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 2.5 times ULN
  • Alkaline phosphatase < 2.5 times ULN
  • Creatinine < 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy
  • No known hypersensitivity to epothilones
  • No peripheral neuropathy > grade 1
  • No unresolved diarrhea within the past 7 days

    • Grade 0 diarrhea required at study entry
  • No concurrent serious medical illness (e.g., HIV positivity or active hepatitis B or C)
  • No severe cardiac insufficiency (e.g., New York Heart Association class III-IV heart disease) with uncontrolled and/or unstable cardiac or coronary artery disease
  • No active or suspected acute or chronic uncontrolled infection, including abscess or fistulae
  • No other malignancy within the past 3 years except curatively treated nonmelanoma skin cancer, prostate cancer, or carcinoma in situ of the cervix
  • No history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits
  • No contraindications to MRI, including any of the following:

    • Pacemaker
    • Ferromagnetic implants
    • Claustrophobia
    • Extreme obesity

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 2 weeks since prior noncytotoxic drugs (e.g., small molecule-targeted drugs) and recovered
  • More than 3 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • More than 3 weeks since prior intracranial surgery and recovered
  • More than 4 weeks since prior radiotherapy and recovered
  • More than 4 weeks since prior major surgery
  • More than 28 days since prior investigational compounds or drugs
  • No prior epothilones
  • No concurrent known diarrheagenic agents
  • No other concurrent anticancer agents, including investigational agents, biological agents, or chemotherapy
  • No other concurrent experimental therapies
  • Concurrent hormone therapy and/or trastuzumab (Herceptin®) allowed
  • No concurrent Coumadin® or other agents containing warfarin

    • Low dose Coumadin® (≤ 1 mg) for prophylactic maintenance of indwelling lines or ports allowed
  • No concurrent radiotherapy for central metastases (e.g., vertebral or mediastinal metastases)

    • Concurrent radiotherapy for local peripheral metastases not being used as marker lesions allowed
  • No concurrent prophylactic hematopoietic growth factors during course 1
  • No concurrent herbal or nontraditional medications
  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: NCT00450866

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
David Peereboom, MD
Investigators
Principal Investigator: David M. Peereboom, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Principal Investigator: Joseph Baar, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: David Peereboom, MD, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00450866     History of Changes
Other Study ID Numbers: CASE5106, P30CA043703, MSKCC-07036
Study First Received: March 20, 2007
Results First Received: July 26, 2013
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
recurrent breast cancer
stage IV breast cancer
tumors metastatic to brain
leptomeningeal metastases
male breast cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Breast Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Breast Diseases
Skin Diseases
Epothilone B
Epothilones
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014