Clinical trial NCT00450866: Epothilone B in Treating Patients With CNS Metastases From Breast Cancer
Official title: Phase II Trial of Patupilone in Patients With Brain Metastases From Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Cancer
Keywords: recurrent breast cancer
stage IV breast cancer
tumors metastatic to brain
leptomeningeal metastases
male breast cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-03-22
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Central Nervous System (CNS) Progression-free Survival(PFS)
timeFrame: 3 months after treatment
Secondary outcomes:
measure: Toxicity as Measured by NCI CTCAE v3.0
timeFrame: 3 months after treatment
measure: CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria
timeFrame: 3 months after treatment
measure: Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria
timeFrame: 3 months after treatment
measure: Overall Survival
timeFrame: 48 months from start of study
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: David M. Peereboom, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Joseph Baar, MD
role: PRINCIPAL_INVESTIGATOR
References: