Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer
|Central Nervous System Metastases Leptomeningeal Metastases Recurrent Breast Cancer Stage IV Breast Cancer Tumors Metastatic to Brain||Drug: methotrexate Drug: liposomal cytarabine Other: quality-of-life assessment Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of the Combination of High-Dose Methotrexate and Intrathecal Liposomal Cytarabine in Patients With Leptomeningeal Metastases With or Without Parenchymal Brain Involvement|
- Survival Free of Neurological Progression, Measured in Weeks [ Time Frame: Time from start of therapy, assessed up to 4 years ]Neurological progression defined by either clinical impression (measured by Karnofsky Performance Status), radiographical response (using Macdonald criteria), or cytologic response (measured by CSF cytology).
- Overall Survival [ Time Frame: Time from start of therapy until death, assessed up to 4 years ]
|Study Start Date:||April 2011|
|Study Completion Date:||October 2014|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (liposomal cytarabine, high-dose methotrexate)
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Other Names:Drug: liposomal cytarabine
Given IT or via LP
Other Names:Other: quality-of-life assessment
Other Name: quality of life assessmentOther: laboratory biomarker analysis
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I. To show that treatment with high-dose methotrexate (HD-MTX) in combination with intrathecal (IT) sustained-release cytarabine (liposomal cytarabine) will result in median progression-free survival (PFS) greater than 7 weeks for patients with breast cancer and leptomeningeal metastases with or without parenchymal brain involvement.
I. To describe the overall survival of patients with central nervous system (CNS) metastatic breast cancer treated with the combination of intravenous (IV) HD-MTX and IT Depocyt (liposomal cytarabine).
II. To describe the safety of the combination therapy, in terms of toxicity, adverse events, and the need for dose reductions or schedule modification.
III. To estimate the best overall response rate achieved during treatment with IV HD-MTX and IT Depocyt. Radiographic response will be measured by the Macdonald Criteria using imaging (magnetic resonance imaging [MRI]), and cytologic response will be measured by cerebrospinal fluid (CSF) cytology.
IV. To determine the number of treatment cycles needed to achieve radiographic and cytologic response.
V. To describe response duration in patients who achieve at least partial radiographic response and cytologic clearance.
VI. To define time to clinical progression as measured by Karnofsky performance status (KPS) and neurological exam.
VII. To describe functional status and quality of life of patients, through clinical evaluations of neurological status and patient-reported quality of life (QOL) measured by the Functional Assessment of Chronic Illness Therapy (FACIT) brain and/or CNS questionnaires.
VIII. To correlate response rates with the extent of patient's systemic disease and tumor receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [Her2]/neu and/or breast cancer, early onset [BRCA] if applicable).
INDUCTION THERAPY (WEEKS 1-6): Patients liposomal cytarabine IT or via lumbar puncture (LP) every 14 days beginning in week 1. Patients also receive high-dose methotrexate IV every 14 days beginning in week 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY (WEEKS 7-11): Patients achieving complete response (CR), partial response (PR), or stable disease (SD) and CSF negative for malignant cells receive liposomal cytarabine IT or via LP beginning in week 7 and high-dose methotrexate IV beginning in week 8. Treatment repeats every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY (WEEKS 13-37): Patients achieving CR, PR, or SD and CSF negative for malignant cells receive liposomal cytarabine IT or via LP every 4 weeks beginning in week 13 and high-dose methotrexate IV monthly beginning in week 15. Treatment with liposomal cytarabine repeats every 4 weeks for up to 5 courses and treatment with high-dose methotrexate repeats monthly for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00992602
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Maciej Mrugala||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|