Clinical trial NCT00992602
Conditions: Central Nervous System Metastases Leptomeningeal Metastases Recurrent Breast Cancer Stage IV Breast Cancer Tumors Metastatic to Brain
Sponsor: University of Washington
Start date: 2011-04-01; Completion date: 2014-10-01
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Detailed description:
PRIMARY OBJECTIVES:

I. To show that treatment with high-dose methotrexate (HD-MTX) in combination with intrathecal (IT) sustained-release cytarabine (liposomal cytarabine) will result in median progression-free survival (PFS) greater than 7 weeks for patients with breast cancer and leptomeningeal metastases with or without parenchymal brain involvement.

SECONDARY OBJECTIVES:

I. To describe the overall survival of patients with central nervous system (CNS) metastatic breast cancer treated with the combination of intravenous (IV) HD-MTX and IT Depocyt (liposomal cytarabine).

II. To describe the safety of the combination therapy, in terms of toxicity, adverse events, and the need for dose reductions or schedule modification.

III. To estimate the best overall response rate achieved during treatment with IV HD-MTX and IT Depocyt. Radiographic response will be measured by the Macdonald Criteria using imaging (magnetic resonance imaging \[MRI\]), and cytologic response will be measured by cerebrospinal fluid (CSF) cytology.

IV. To determine the number of treatment cycles needed to achieve radiographic and cytologic response.

V. To describe response duration in patients who achieve at least partial radiographic response and cytologic clearance.

VI. To define time to clinical progression as measured by Karnofsky performance status (KPS) and neurological exam.

VII. To describe functional status and quality of life of patients, through clinical evaluations of neurological status and patient-reported quality of life (QOL) measured by the Functional Assessment of Chronic Illness Therapy (FACIT) brain and/or CNS questionnaires.

VIII. To correlate response rates with the extent of patient's systemic disease and tumor receptor status (estrogen receptor \[ER\], progesterone receptor \[PR\], human epidermal growth factor receptor 2 \[Her2\]/neu and/or breast cancer, early onset \[BRCA\] if applicable).

OUTLINE:

INDUCTION THERAPY (WEEKS 1-6): Patients liposomal cytarabine IT or via lumbar puncture (LP) every 14 days beginning in week 1. Patients also receive high-dose methotrexate IV every 14 days beginning in week 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY (WEEKS 7-11): Patients achieving complete response (CR), partial response (PR), or stable disease (SD) and CSF negative for malignant cells receive liposomal cytarabine IT or via LP beginning in week 7 and high-dose methotrexate IV beginning in week 8. Treatment repeats every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY (WEEKS 13-37): Patients achieving CR, PR, or SD and CSF negative for malignant cells receive liposomal cytarabine IT or via LP every 4 weeks beginning in week 13 and high-dose methotrexate IV monthly beginning in week 15. Treatment with liposomal cytarabine repeats every 4 weeks for up to 5 courses and treatment with high-dose methotrexate repeats monthly for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Arms: arm 1: See Detailed Description
Interventions: intervention 1: methotrexate intervention 2: liposomal cytarabine intervention 3: quality-of-life assessment intervention 4: laboratory biomarker analysis
Intervention descriptions: intervention 1: Given IV intervention 2: Given IT or via LP intervention 3: Ancillary studies intervention 4: Correlative studies

Protocol documents: