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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00992602
First received: October 7, 2009
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Central Nervous System Metastases
Leptomeningeal Metastases
Recurrent Breast Cancer
Stage IV Breast Cancer
Tumors Metastatic to Brain
Drug: methotrexate
Drug: liposomal cytarabine
Other: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Combination of High-Dose Methotrexate and Intrathecal Liposomal Cytarabine in Patients With Leptomeningeal Metastases With or Without Parenchymal Brain Involvement

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Survival free of neurological progression, measured in weeks [ Time Frame: Time from start of therapy, assessed up to 4 years ] [ Designated as safety issue: No ]
    Described using Kaplan-Meier survival curves, and confidence intervals for median PFS will be computed.

  • Number and percent of patients reporting grade 3+ neurological and systemic adverse events that persists following dose reductions or schedule modifications, assessed using Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Time from start of therapy until death, assessed up to 4 years ] [ Designated as safety issue: No ]
    Described using Kaplan-Meier survival curves. Measured as time from start of therapy until death, censored on the last date the patient was known to be alive.

  • Radiographic response, measured by RECIST using imaging [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Best overall response rate and a 90% Wilson score binomial confidence interval will be determined for evaluable subjects.

  • Cytologic response as measured by CSF cytology (positive or negative for malignant cells) [ Time Frame: Up to week 37 ] [ Designated as safety issue: No ]
  • Functional Assessment of Cancer Therapy (FACT)-Brain (Br)/CNS total score and subscales (physical well-being, social/family well-being, emotional well-being, functional well-being, symptom index) using standard scoring [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    FACT-BR/CNS total score and subscales will be examined longitudinally for the full study cohort, and for groups defined by length of follow-up (pattern-mixture model), using linear mixed effects regression.


Estimated Enrollment: 22
Study Start Date: April 2011
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (liposomal cytarabine, high-dose methotrexate)
See Detailed Description
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: liposomal cytarabine
Given IT or via LP
Other Names:
  • cytarabine liposome
  • DepoCyt
  • DepoCyte
  • DepoFoam-encapsulated cytarabine
  • DTC 101
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992602

Locations
United States, California
University of California Medical Center At Irvine-Irvine Campus Recruiting
Irvine, California, United States, 92697
Contact: Daniela A. Bota    877-827-8839    ucstudy@uci.edu   
Principal Investigator: Daniela A. Bota         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Maciej M. Mrugala    206-598-9487      
Principal Investigator: Maciej M. Mrugala         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Maciej Mrugala Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00992602     History of Changes
Other Study ID Numbers: 6954, NCI-2009-01309, 6954, P30CA015704
Study First Received: October 7, 2009
Last Updated: September 16, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Meningeal Carcinomatosis
Neoplasm Metastasis
Neoplasms, Second Primary
Breast Diseases
Central Nervous System Neoplasms
Meningeal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Nervous System Diseases
Nervous System Neoplasms
Pathologic Processes
Skin Diseases
Cytarabine
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 21, 2014