Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
OBJECTIVES:
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Determine the cerebrospinal fluid (CSF):plasma ratio of pemetrexed disodium at different IV dose levels in patients with leptomeningeal metastases.
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Determine the safety of this drug in these patients.
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Determine the antitumor activity of this drug in these patients.
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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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium [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. [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. [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. [Prior to dose one]
Patients will have a one time blood draw to look at serum biomarkers prior to dose one.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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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
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Patients may have brain metastases in addition to LM
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Patients with clinically significant interstitial fluid with effusion controlled by drainage are eligible
PATIENT CHARACTERISTICS:
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Karnofsky performance status 60-100%
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Life expectancy > 2 months
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Creatinine clearance ≥ 45 mL/min
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Bilirubin < 1.5 times upper limit of normal (ULN)
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Transaminases < 3.0 times ULN (5 times ULN for hepatic metastasis)
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WBC > 3,000/mm³
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Neutrophil count > 1,500/mm³
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Platelet count > 100,000/mm³
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Hemoglobin > 10 g/dL
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception during and for 3 months after completion of study treatment
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Able to undergo lumbar puncture (i.e., no noncommunicating hydrocephalus or spinal block) or has an Ommaya reservoir in place
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Able to take steroids, cyanocobalamin (vitamin B12), and folic acid
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No other active cancer except nonmelanoma skin cancer or carcinoma in situ of the cervix
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Patients with prior malignancies who are in complete remission and are off all therapy for that malignancy for ≥ 3 years are eligible
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No significant medical or psychiatric illness that would interfere with study compliance
PRIOR CONCURRENT THERAPY:
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More than 2 weeks since prior radiotherapy and recovered
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No concurrent radiotherapy
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No nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid within 2 days before or after study treatment (5 days for long-acting NSAIDs)
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No other concurrent cytotoxic chemotherapy
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Concurrent hormonal or biological therapy allowed
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago | Illinois | United States | 60611-3013 |
Sponsors and Collaborators
- Northwestern University
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jeffrey J. Raizer, MD, Robert H. Lurie Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NU 06C2
- STU00004482