Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer
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ClinicalTrials.gov Identifier: NCT00992602 |
Recruitment Status :
Completed
First Posted : October 9, 2009
Results First Posted : July 7, 2017
Last Update Posted : July 7, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
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 Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 3 participants |
Allocation: | N/A |
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 |
Study Start Date : | April 2011 |
Actual Primary Completion Date : | June 2013 |
Actual Study Completion Date : | October 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment (liposomal cytarabine, high-dose methotrexate)
See Detailed Description
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Drug: methotrexate
Given IV
Other Names:
Drug: liposomal cytarabine Given IT or via LP
Other Names:
Other: quality-of-life assessment Ancillary studies
Other Name: quality of life assessment Other: laboratory biomarker analysis Correlative studies |
- 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 ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Women who are not pregnant (contraception must be used throughout the study)
- Diagnosis of breast cancer with metastases to CNS (regardless of receptor status); leptomeningeal disease must be present with/without parenchymal brain involvement
- Able to provide informed consent
- No prior treatment with whole brain radiotherapy (WBRT); if patient received stereotactic radiosurgery (SRS) prior to enrollment it must be well documented which lesions were treated and untreated index lesions for follow up must be identified; no treatment with SRS will be permitted while on the study; CNS disease must be documented by MRI and CSF cytology
- Karnofsky Performance Status > 60
- White blood cells (WBC) >= 3.0 K
- Absolute neutrophil count (ANC) >= 1.5 K
- Platelets (PLT) >= 100 K
- Hematocrit (HCT) >= 30%
- Glomerular filtration rate (GFR) >= 60 mL/min
- Acceptable liver function (see exclusion criteria)
- Any ongoing therapy for systemic disease allows for the addition of systemic HD-MTX and IT Depocyt; in general patients receiving trastuzumab or lapatinib at the time of enrollment will be allowed to continue; bisphosphonates (i.e., zoledronic acid) and denosumab will be allowed; other non-CNS active chemotherapies might be allowed if no known interactions with study drugs are present; this must be reviewed and approved by the primary investigator on a case-by-case basis
- Mini-mental state examination score of 24 or above
Exclusion Criteria:
- Serum bilirubin > 1.5 x the upper limit of reference range (ULRR)
- Serum creatinine > 1.5 x ULRR or creatinine clearance =< 60 mL/minute (calculated by Cockcroft-Gault formula)
- Potassium, < 3.7 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULRR
- Alkaline phosphatase (ALP) > 2.5 x ULRR or > 5 x ULRR if judged by the investigator to be related to liver metastases
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- Patients with known pleural effusion or ascites
- Prior treatment with whole brain radiotherapy (prior treatment with SRS is allowed under conditions provided in the inclusion criteria)
- Previous allergic or adverse reaction to methotrexate or cytarabine
- Prior treatment with systemic HD-MTX, IT liposomal cytarabine, or IT therapy of any kind
- Prior IT therapy of any kind
- Women who are currently pregnant or breast feeding
- Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Receipt of any investigational agents within 30 days prior to commencing study treatment
- Last dose of prior chemotherapy was less than 4 weeks before the start of study therapy; patients who had no toxicities with prior chemotherapy can start study treatment earlier than 4 weeks
- Stereotactic radiosurgery (SRS) less than 2 weeks before the start of study therapy
- Any unresolved toxicity greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy
- Previous enrollment in the present study
- Major surgery within 4 weeks prior to starting therapy, with the exception of the Ommaya reservoir which can be used for introduction of chemotherapy within 48-72 hours after placement

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 |
Responsible Party: | Maciej Mrugala, Principal Investigator, University of Washington |
ClinicalTrials.gov Identifier: | NCT00992602 |
Other Study ID Numbers: |
6954 NCI-2009-01309 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 6954 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium ) P30CA015704 ( U.S. NIH Grant/Contract ) |
First Posted: | October 9, 2009 Key Record Dates |
Results First Posted: | July 7, 2017 |
Last Update Posted: | July 7, 2017 |
Last Verified: | June 2017 |
Cytarabine Methotrexate Breast Neoplasms Neoplasm Metastasis Neoplasms, Second Primary Meningeal Carcinomatosis Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Neoplastic Processes Pathologic Processes Meningeal Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms |
Nervous System Diseases Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents |