Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease
Primary Purpose
Leptomeningeal Metastases
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
pharmacological study
methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Leptomeningeal Metastases focused on measuring unspecified adult solid tumor, protocol specific
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (intraventricular chemotherapy)
Arm Description
Patients receive intraventricular methotrexate continuously on days 1-14. Treatment continues in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Efficacy of continuously delivered intraventricular methotrexate
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
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
Toxicities of continuous intraventricular methotrexate infusion
Pharmacodynamics of continuously delivered intraventricular methotrexate
Full Information
NCT ID
NCT01438021
First Posted
September 19, 2011
Last Updated
November 8, 2012
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01438021
Brief Title
Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease
Official Title
Characterization of the Pharmacokinetics and Efficacy of Intraventricular Methotrexate Continuously Delivered Via a Mini Pump for Treatment of Leptomeningeal Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of funding
Study Start Date
September 2012 (undefined)
Primary Completion Date
November 2013 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leptomeningeal Metastases
Keywords
unspecified adult solid tumor, protocol specific
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (intraventricular chemotherapy)
Arm Type
Experimental
Arm Description
Patients receive intraventricular methotrexate continuously on days 1-14. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
amethopterin, Folex, methylaminopterin, Mexate, MTX
Intervention Description
Given intraventricularly
Primary Outcome Measure Information:
Title
Efficacy of continuously delivered intraventricular methotrexate
Description
The concentration of methotrexate in the brain parenchyma will be determined with microdialysis probe placed next to the ventricle.
Time Frame
Day 3 after start of treatment
Title
Pharmacokinetics of continuous intraventricular infusion of methotrexate
Description
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.
Time Frame
Day 14 after start of treatment
Secondary Outcome Measure Information:
Title
Response rate of continuous intraventricular methotrexate infusion
Time Frame
Day 42 after start of treatment
Title
Toxicities of continuous intraventricular methotrexate infusion
Time Frame
Day 3 after start of treatment
Title
Pharmacodynamics of continuously delivered intraventricular methotrexate
Time Frame
Day 42 after start of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mike Chen, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease
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