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Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00992602
Recruitment Status : Completed
First Posted : October 9, 2009
Results First Posted : July 7, 2017
Last Update Posted : July 7, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Maciej Mrugala, University of Washington

Brief Summary:
This phase II trial studies how well giving liposomal cytarabine and high-dose methotrexate works in treating patients with breast cancer that has spread to the central nervous system. Drugs used in chemotherapy, such as liposomal cytarabine and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving liposomal cytarabine with high-dose methotrexate may kill more tumor cells.

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

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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

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment (liposomal cytarabine, high-dose methotrexate)
See Detailed Description
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

Drug: liposomal cytarabine
Given IT or via LP
Other Names:
  • cytarabine liposome
  • DepoCyt
  • DepoCyte
  • DepoFoam-encapsulated cytarabine
  • DTC 101

Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Time from start of therapy until death, assessed up to 4 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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

Information from the National Library of Medicine

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 identifier (NCT number): NCT00992602

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United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
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Principal Investigator: Maciej Mrugala Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Responsible Party: Maciej Mrugala, Principal Investigator, University of Washington 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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Meningeal Carcinomatosis
Neoplasms by Site
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
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents