Clinical Trial Detail

This phase II trial is studying how well giving high-dose methotrexate together with liposomal cytarabine works in treating patients with central nervous system (CNS) metastases from metastatic breast cancer. Drugs used in chemotherapy, such as methotrexate and liposomal cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving high-dose systemic methotrexate with intra-cerebral spinal fluid (CSF) liposomal cytarabine may kill more tumor cells.

Ages Eligible for Study: 18 Years and older

Genders Eligible for Study: Female

- 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

- Ability 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 index lesions (untreated) for follow up must be identified, no treatment with SRS will be permitted while on the study

- CNS disease must be documented by magnetic resonance imaging (MRI) and cerebrospinal fluid (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%

- Acceptable renal function (glomerular filtration rate [GFR] >= 60 mL/min)

- Acceptable liver function (see exclusion criteria)

- Well controlled systemic disease

- Therapy for systemic disease allowing for 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 will be reviewed on case-by-case basis

- Mini-mental status examination score of 24 or above

Other eligibility criteria may apply.

- 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 > 5x 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 stereotactic radiosurgery (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 or IT liposomal cytarabine

- 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 discontinued 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

- Last radiation therapy to the brain in the form of SRS within the last 2 weeks before the start of study therapy

- Any unresolved toxicity greater than Common Toxicity Criteria (CTC) grade 1 from previous anti-cancer therapy

- Previous enrollment in the present study

- Major surgery within 4 weeks prior to starting therapy, Ommaya reservoir can be used for introduction of chemotherapy within 48-72 hours after placement

Other exclusion criteria may apply.

Updated data copied from CT.gov (sy)