Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease

Leptomeningeal Metastases Clinical Trial

Official title:

Characterization of the Pharmacokinetics and Efficacy of Intraventricular Methotrexate Continuously Delivered Via a Mini Pump for Treatment of Leptomeningeal Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01438021
• Other study ID #: 09201
• Secondary ID: NCI-2011-03006
• Status: Withdrawn
• Phase: N/A
• First received: September 19, 2011
• Last updated: November 8, 2012
• Start date: September 2012

Study information

• Verified date: November 2012
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leptomeningeal Metastases
• Meningeal Carcinomatosis

Intervention

Other:
• pharmacological study
Correlative studies

Drug:
• methotrexate
Given intraventricularly

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 3 after start of treatment	No
Primary	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.	Day 14 after start of treatment	No
Secondary	Response rate of continuous intraventricular methotrexate infusion		Day 42 after start of treatment	No
Secondary	Toxicities of continuous intraventricular methotrexate infusion		Day 3 after start of treatment	Yes
Secondary	Pharmacodynamics of continuously delivered intraventricular methotrexate		Day 42 after start of treatment	No