Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer
Central Nervous System Metastases
Recurrent Breast Cancer
Stage IV Breast Cancer
Tumors Metastatic to Brain
Drug: liposomal cytarabine
Other: quality-of-life assessment
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]Described using Kaplan-Meier survival curves, and confidence intervals for median PFS will be computed.
- Number and percent of patients reporting grade 3+ neurological and systemic adverse events that persists following dose reductions or schedule modifications, assessed using Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: Time from start of therapy until death, assessed up to 4 years ] [ Designated as safety issue: No ]Described using Kaplan-Meier survival curves. Measured as time from start of therapy until death, censored on the last date the patient was known to be alive.
- Radiographic response, measured by RECIST using imaging [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Best overall response rate and a 90% Wilson score binomial confidence interval will be determined for evaluable subjects.
- Cytologic response as measured by CSF cytology (positive or negative for malignant cells) [ Time Frame: Up to week 37 ] [ Designated as safety issue: No ]
- Functional Assessment of Cancer Therapy (FACT)-Brain (Br)/CNS total score and subscales (physical well-being, social/family well-being, emotional well-being, functional well-being, symptom index) using standard scoring [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]FACT-BR/CNS total score and subscales will be examined longitudinally for the full study cohort, and for groups defined by length of follow-up (pattern-mixture model), using linear mixed effects regression.
|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)
See Detailed Description
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, California|
|University of California Medical Center At Irvine-Irvine Campus|
|Irvine, California, United States, 92697|
|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|