Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
This trial is active, not recruiting.
|Conditions||brain and central nervous system tumors, chronic myeloproliferative disorders, leukemia, lymphoma, lymphoproliferative disorder, metastatic cancer, multiple myeloma and plasma cell neoplasm, myelodysplastic syndromes, precancerous condition, secondary myelofibrosis, unspecified adult solid tumor, protocol specific|
|Collaborator||National Cancer Institute (NCI)|
|Start date||January 2007|
|End date||March 2016|
|Trial size||15 participants|
|Trial identifier||NCT00424242, NU 06C2, STU00004482|
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.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Escalating doses of Pemetrexed beginning at 500 mg/m2
Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium
time frame: 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.
To determine the safety of Pemetrexed in patients with LM.
time frame: After every 2 doses approximately 6 weeks
To assess the role of serum biomarkers in patients with LM.
time frame: Prior to dose one
Male or female participants at least 18 years old.
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
|Official title||A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases|
|Principal investigator||Jeffrey J. Raizer, MD|
|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.|
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