A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
- 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium
Patients will have CSF collected approximately every 6 weeks for assessment while on study.
Every 6 weeks for assessment while on study.
Jeffrey J. Raizer, MD
Robert H. Lurie Cancer Center
United States: Food and Drug Administration
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|