Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease

Not Applicable

Withdrawn

• Conditions: Leptomeningeal Metastases
• Interventions: Other: pharmacological study; Drug: methotrexate

• Registration Number: NCT01438021
• Lead Sponsor: City of Hope Medical Center

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.

Study Timeline

• Study First Submitted: 2011-09-19
• Study First Submitted QC: 2011-09-19
• Study First Posted: 2011-09-21
• Study Start: 2012-09
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-08
• Last Update Posted: 2012-11-09
• Primary Completion: 2013-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (intraventricular chemotherapy)	pharmacological study	Patients receive intraventricular methotrexate continuously on days 1-14. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (intraventricular chemotherapy)	methotrexate	Patients receive intraventricular methotrexate continuously on days 1-14. Treatment continues in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Efficacy of continuously delivered intraventricular methotrexate	Day 3 after start of treatment	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	Day 14 after start of treatment	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

Name	Time	Method
Response rate of continuous intraventricular methotrexate infusion	Day 42 after start of treatment
Toxicities of continuous intraventricular methotrexate infusion	Day 3 after start of treatment
Pharmacodynamics of continuously delivered intraventricular methotrexate	Day 42 after start of treatment