Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

September 3, 2021 updated by: Northwestern University

A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

RATIONALE: Pemetrexed disodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Studying samples of cerebrospinal fluid and blood from patients with cancer in the laboratory may help doctors learn how pemetrexed disodium works in the body and identify biomarkers related to cancer.

PURPOSE: This clinical trial is studying the side effects and how well pemetrexed disodium works in treating patients with leptomeningeal metastases.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the cerebrospinal fluid (CSF):plasma ratio of pemetrexed disodium at different IV dose levels in patients with leptomeningeal metastases.
  • Determine the safety of this drug in these patients.
  • Determine the antitumor activity of this drug in these patients.
  • Assess the role of CSF vascular endothelial growth factor and YKL 40 as markers of response and/or prognosis in these patients.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo lumbar puncture and blood collection prior to therapy and 30-60 minutes after the first dose of pemetrexed disodium for pharmacological studies. Patients with Ommaya reservoirs undergo cerebrospinal fluid (CSF) collection at baseline and 0.25, 0.50, 1, 2, 4, 6 and 8.0 hours after pemetrexed disodium administration. CSF is then obtained once during each subsequent course of study treatment. CSF and blood are also evaluated for YKL 40 and vascular endothelial growth factor.

After completion of study therapy, patients are followed every 2-3 months.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

15

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of systemic malignancy (solid tumor or hematologic malignancy) or primary CNS lymphoma with leptomeningeal metastases (LM) as documented by MRI, cerebrospinal fluid, or both
  • Patients may have brain metastases in addition to LM
  • Patients with clinically significant interstitial fluid with effusion controlled by drainage are eligible

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 2 months
  • Creatinine clearance ≥ 45 mL/min
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • Transaminases < 3.0 times ULN (5 times ULN for hepatic metastasis)
  • WBC > 3,000/mm³
  • Neutrophil count > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 10 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Able to undergo lumbar puncture (i.e., no noncommunicating hydrocephalus or spinal block) or has an Ommaya reservoir in place
  • Able to take steroids, cyanocobalamin (vitamin B12), and folic acid
  • No other active cancer except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • Patients with prior malignancies who are in complete remission and are off all therapy for that malignancy for ≥ 3 years are eligible
  • No significant medical or psychiatric illness that would interfere with study compliance

PRIOR CONCURRENT THERAPY:

  • More than 2 weeks since prior radiotherapy and recovered
  • No concurrent radiotherapy
  • No nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid within 2 days before or after study treatment (5 days for long-acting NSAIDs)
  • No other concurrent cytotoxic chemotherapy
  • Concurrent hormonal or biological therapy allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Escalating doses of Pemetrexed
Escalating doses of Pemetrexed beginning at 500 mg/m2
Drug: Pemetrexed
Orally beginning at 500 mg/m2 every 3 weeks until disease progression
Other Names:
  • Alimta
  • LY231514

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium
Time Frame: Every 6 weeks for assessment while on study.
Patients will have CSF collected approximately every 6 weeks for assessment while on study.
Every 6 weeks for assessment while on study.
To determine whether there is any anti-tumor activity against LM with Pemetrexed.
Time Frame: Every six weeks.
Patients will have a scan every six weeks to assess tumor response.
Every six weeks.
To determine the safety of Pemetrexed in patients with LM.
Time Frame: After every 2 doses approximately 6 weeks
Adverse events will be collected every six weeks during patient visits.
After every 2 doses approximately 6 weeks
To assess the role of serum biomarkers in patients with LM.
Time Frame: Prior to dose one
Patients will have a one time blood draw to look at serum biomarkers prior to dose one.
Prior to dose one

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (ACTUAL)

January 1, 2010

Study Completion (ACTUAL)

September 1, 2011

Study Registration Dates

First Submitted

January 16, 2007

First Submitted That Met QC Criteria

January 16, 2007

First Posted (ESTIMATE)

January 18, 2007

Study Record Updates

Last Update Posted (ACTUAL)

September 8, 2021

Last Update Submitted That Met QC Criteria

September 3, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NU 06C2
  • STU00004482 (OTHER: Northwestern University IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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