Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer
Condition: Central Nervous System Metastases; Leptomeningeal Metastases; Recurrent Breast Cancer; Stage IV Breast Cancer; Tumors Metastatic to Brain
MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Meningeal Carcinomatosis
Intervention: methotrexate; liposomal cytarabine; quality-of-life assessment; laboratory biomarker analysis
Intervention description: Given IV; Given IT or via LP; Ancillary studies; Correlative studies
Intervention MeSH terms: Cytarabine; Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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