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Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University Identifier:
First received: January 16, 2007
Last updated: March 15, 2017
Last verified: March 2017

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 Intervention Phase
Brain and Central Nervous System Tumors
Chronic Myeloproliferative Disorders
Lymphoproliferative Disorder
Metastatic Cancer
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Precancerous Condition
Secondary Myelofibrosis
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Pemetrexed
Early Phase 1

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • 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.

Estimated Enrollment: 15
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)
Arms Assigned Interventions
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

Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
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Please refer to this study by its identifier: NCT00424242

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Principal Investigator: Jeffrey J. Raizer, MD Robert H. Lurie Cancer Center
  More Information

Responsible Party: Northwestern University Identifier: NCT00424242     History of Changes
Other Study ID Numbers: NU 06C2
STU00004482 ( Other Identifier: Northwestern University IRB )
Study First Received: January 16, 2007
Last Updated: March 15, 2017

Keywords provided by Northwestern University:
unspecified adult solid tumor, protocol specific
tumors metastatic to brain
leptomeningeal metastases
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma
meningeal chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic neutrophilic leukemia
essential thrombocythemia
polycythemia vera
recurrent adult acute lymphoblastic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
previously treated myelodysplastic syndromes
secondary acute myeloid leukemia
acute undifferentiated leukemia
mast cell leukemia
recurrent adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
T-cell large granular lymphocyte leukemia
atypical chronic myeloid leukemia, BCR-ABL negative
stage IV chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
chronic myelomonocytic leukemia

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm Metastasis
Myelodysplastic Syndromes
Primary Myelofibrosis
Nervous System Neoplasms
Central Nervous System Neoplasms
Myeloproliferative Disorders
Lymphoproliferative Disorders
Precancerous Conditions
Meningeal Carcinomatosis
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders processed this record on April 28, 2017