Epothilone B in Treating Patients With CNS Metastases From Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase II Trial of Patupilone in Patients With Brain Metastases From Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00450866
• Other study ID #: CASE5106
• Secondary ID: P30CA043703MSKCC
• Status: Completed
• Phase: Phase 2
• First received: March 20, 2007
• Last updated: January 28, 2014
• Start date: January 2007
• Est. completion date: May 2012

Study information

• Verified date: January 2014
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: May 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
David Peereboom, MD	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central Nervous System (CNS) Progression-free Survival(PFS)	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.	3 months after treatment	No
Secondary	Toxicity as Measured by NCI CTCAE v3.0	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.	3 months after treatment	Yes
Secondary	CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria	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)	3 months after treatment	No
Secondary	Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria	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)	3 months after treatment	No
Secondary	Overall Survival	Median time (months) that patients survived during the duration of the study.	48 months from start of study	No