Pemetrexed Disodium 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.
Brain and Central Nervous System Tumors
Chronic Myeloproliferative Disorders
Multiple Myeloma and Plasma Cell Neoplasm
Unspecified Adult Solid Tumor, Protocol Specific
Early Phase 1
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases|
- 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.
- 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.
- 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.
- 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.
|Study Start Date:||January 2007|
|Estimated Study Completion Date:||March 2020|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Experimental: Escalating doses of Pemetrexed
Escalating doses of Pemetrexed beginning at 500 mg/m2
Orally beginning at 500 mg/m2 every 3 weeks until disease progression
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00424242
|United States, Illinois|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University|
|Chicago, Illinois, United States, 60611-3013|
|Principal Investigator:||Jeffrey J. Raizer, MD||Robert H. Lurie Cancer Center|