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

Central Nervous System Metastases research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Central Nervous System Metastases

Leptomeningeal Metastases

Recurrent Breast Cancer

Stage IV Breast Cancer

Tumors Metastatic to Brain

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:methotrexateGiven IV

Drug:liposomal cytarabineGiven IT or via LP

Other:quality-of-life assessmentAncillary studies

Other:laboratory biomarker analysisCorrelative studies

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Treatment (liposomal cytarabine, high-dose methotrexate)See Detailed Description

Study Status


Start Date: April 2011

Completed Date: October 2014

Phase: Phase 2

Type: Interventional


Primary Outcome: Survival Free of Neurological Progression, Measured in Weeks

Secondary Outcome: Overall Survival

Study sponsors, principal investigator, and references

Principal Investigator: Maciej Mrugala

Lead Sponsor: University of Washington

Collaborator: National Cancer Institute (NCI)

More information:

Discuss Methotrexate