Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease

This study has been withdrawn prior to enrollment.
(Lack of funding)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01438021
First received: September 19, 2011
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

This pilot clinical trial studies continuous intraventricular methotrexate in treating patients with leptomeningeal disease. Drugs used in chemotherapy, such as methotrexate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving drugs directly into the ventricles may be an effective treatment for patients with leptomeningeal disease


Condition Intervention
Leptomeningeal Metastases
Other: pharmacological study
Drug: methotrexate

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Characterization of the Pharmacokinetics and Efficacy of Intraventricular Methotrexate Continuously Delivered Via a Mini Pump for Treatment of Leptomeningeal Disease

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Efficacy of continuously delivered intraventricular methotrexate [ Time Frame: Day 3 after start of treatment ] [ Designated as safety issue: No ]
    The concentration of methotrexate in the brain parenchyma will be determined with microdialysis probe placed next to the ventricle.

  • Pharmacokinetics of continuous intraventricular infusion of methotrexate [ Time Frame: Day 14 after start of treatment ] [ Designated as safety issue: No ]
    Determined by measuring brain interstitial levels of methotrexate using microdialysis catheters, lumbar cerebral spinal fluid (CSF) levels (a distant site) of methotrexate via a lumbar drain during the inpatients phase, ventricular CSF levels of methotrexate using the Ommaya reservoir, and systemic levels of methotrexate in the blood.


Secondary Outcome Measures:
  • Response rate of continuous intraventricular methotrexate infusion [ Time Frame: Day 42 after start of treatment ] [ Designated as safety issue: No ]
  • Toxicities of continuous intraventricular methotrexate infusion [ Time Frame: Day 3 after start of treatment ] [ Designated as safety issue: Yes ]
  • Pharmacodynamics of continuously delivered intraventricular methotrexate [ Time Frame: Day 42 after start of treatment ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: September 2012
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (intraventricular chemotherapy)
Patients receive intraventricular methotrexate continuously on days 1-14. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: methotrexate
Given intraventricularly
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the pharmacokinetics and efficacy of continuous intraventricular methotrexate infusion in the treatment of leptomeningeal disease.

SECONDARY OBJECTIVES:

I. Describe the dose limiting toxicities. II. Describe the pharmacodynamics of continuously delivered intraventricular methotrexate.

III. Assess for response.

OUTLINE:

Patients receive intraventricular methotrexate continuously on days 1-14. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with leptomeningeal carcinomatosis (from solid tumors)
  • Subjects with lymphomatous or leukemic meningitis
  • The effects of methotrexate on the developing fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following the conclusion of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she will be excluded from the study and should inform her treating physical immediately
  • Karnofsky Performance Status greater than 70%
  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • We will exclude subjects who have had prior intrathecal/intraventricular therapy with methotrexate within 6 months

Exclusion Criteria:

  • Prior therapy with methotrexate for management of leptomeningeal disease
  • Subjects with evidence of hydrocephalous
  • Subjects with intraparenchymal lesions or bulky disease
  • Subjects with ventriculoperitoneal shunt in place
  • Previous history of whole brain radiation therapy
  • Subjects who, in the opinion of the principal investigator, may not be able to comply with the safety monitoring requirements of the study will not be included in this trial
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01438021

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Mike Chen, MD City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01438021     History of Changes
Other Study ID Numbers: 09201, NCI-2011-03006
Study First Received: September 19, 2011
Last Updated: November 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasm Metastasis
Meningeal Carcinomatosis
Neoplastic Processes
Neoplasms
Pathologic Processes
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014