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

NCT00992602 | Completed Phase 2 Results DMC

• 3 other identifiers: 6954NCI-2009-01309P30CA015704
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Central Nervous System Metastases; Leptomeningeal Metastases; Recurrent Breast Cancer; Stage IV Breast Cancer; Tumors Metastatic to Brain

Outcome Measures

Primary Outcomes (1)

• Survival Free of Neurological Progression, Measured in Weeks

  Neurological progression defined by either clinical impression (measured by Karnofsky Performance Status), radiographical response (using Macdonald criteria), or cytologic response (measured by CSF cytology).

  Time from start of therapy, assessed up to 4 years

Secondary Outcomes (1)

• Overall Survival

  Time from start of therapy until death, assessed up to 4 years

Study Arms (1)

Treatment (liposomal cytarabine, high-dose methotrexate)

EXPERIMENTAL

See Detailed Description

Drug: methotrexate; Drug: liposomal cytarabine; Other: quality-of-life assessment; Other: laboratory biomarker analysis

Interventions

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (liposomal cytarabine, high-dose methotrexate)

liposomal cytarabine DRUG

Given IT or via LP

Also known as: cytarabine liposome, DepoCyt, DepoCyte, DepoFoam-encapsulated cytarabine, DTC 101

Treatment (liposomal cytarabine, high-dose methotrexate)

quality-of-life assessment OTHER

Ancillary studies

Also known as: quality of life assessment

Treatment (liposomal cytarabine, high-dose methotrexate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (liposomal cytarabine, high-dose methotrexate)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis; Breast Neoplasms; Brain Neoplasms

Interventions

Methotrexate; merphos

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Our accrual limitations highlight the challenges of conducting studies in "orphan diseases" such as LC and underscore the importance of multi-center collaboration.

Results Point of Contact

• Title: Maciej M. Mrugala, MD, PhD, MPH
• Organization: University of Washington

mmrugala@uw.edu

206-543-4069

Study Officials

• Maciej Mrugala

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 7, 2009
• First Posted: October 9, 2009
• Study Start: April 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: October 1, 2014
• Last Updated: July 7, 2017
• Results First Posted: July 7, 2017

Record last verified: 2017-06

Locations

US (1)