High-dose Methotrexate and Liposomal Cytarabine in Treating Patients With CNS Metastases From Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 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: January 29, 2014
Last verified: January 2014
  Purpose

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.


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: questionnaire administration
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/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:
  • Progression-free survival (PFS) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Described using Kaplan-Meier survival curves, and confidence intervals for median PFS will be computed. A 95% confidence interval lower bound greater than 7 weeks would be strong evidence for efficacy of the combined treatment regimen. However, an observed median PFS of 12 weeks or greater would also show promise for the combined therapy.

  • Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria grade 3+ neurological and systemic toxicity that persists following dose reductions or schedule modifications [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 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.

  • Duration of response [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Described using Kaplan-Meier survival curves. Radiographic response will be measured by the RECIST criteria.

  • Cytologic response as measured by CSF cytology (positive or negative for malignant cells) [ Time Frame: Up to week 37 ] [ Designated as safety issue: No ]
  • FACT-Brain (Br) total score and subscales (physical well-being, social/family well-being, emotional well-being, functional well-being, symptom index) using standard scoring [ Time Frame: Assessed every 4 weeks until withdrawal from study ] [ Designated as safety issue: No ]

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 (chemotherapy)

INDUCTION THERAPY (weeks 1-6): Patients receive high-dose methotrexate IV over 4 hours on days 1, 15, and 29 and liposomal cytarabine IT or LP over 5 minutes on days 8, 22, and 36.

CONSOLIDATION THERAPY (weeks 7-11): Patients achieving CR, PR, or SD then receive high-dose methotrexate IV over 4 hours on days 43 and 57. Patients also receive liposomal cytarabine IT or LP over 5 minutes on days 50 and 64.

MAINTENANCE THERAPY (weeks 13-37): Patients achieving CR, PR, or SD receive high-dose methotrexate IV over 4 hours once monthly and beginning in week 15, patients receive liposomal cytarabine IT or LP over 5 minutes once monthly. Treatment repeats once monthly for 5-6 courses in the absence of disease progression or unacceptable toxicity.

Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: liposomal cytarabine
Given IT
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: questionnaire administration
Ancillary 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
  • 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)
  • 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

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 > 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
  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, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Suriya Jeyapalan    401-444-1488      
Principal Investigator: Suriya Jeyapalan         
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, P30CA015704
Study First Received: October 7, 2009
Last Updated: January 29, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Meningeal Carcinomatosis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Cytarabine
Methotrexate
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on July 24, 2014