Continuous Intraventricular Methotrexate in Treating Patients With Leptomeningeal Disease

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

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

Study Overview

• Status: Withdrawn
• Conditions: Leptomeningeal Metastases
• Intervention / Treatment: Other: pharmacological study; Drug: methotrexate

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 Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: pharmacological studies; Drug: methotrexate; Given intraventricularly; Other Names: amethopterin; Folex; methylaminopterin; Mexate; MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mike Chen, MD, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ANTICIPATED): November 1, 2013

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 19, 2011
• First Posted (ESTIMATE): September 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 9, 2012
• Last Update Submitted That Met QC Criteria: November 8, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: 09201; NCI-2011-03006 (REGISTRY: CTRP (Clinical Trial Reporting Program))