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A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases


Phase 0
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium

Outcome Description:

Patients will have CSF collected approximately every 6 weeks for assessment while on study.

Outcome Time Frame:

Every 6 weeks for assessment while on study.

Safety Issue:

Yes

Principal Investigator

Jeffrey J. Raizer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Robert H. Lurie Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NU 06C2

NCT ID:

NCT00424242

Start Date:

January 2007

Completion Date:

March 2015

Related Keywords:

  • 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
  • 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
  • refractory hairy cell leukemia
  • prolymphocytic leukemia
  • stage IV mycosis fungoides/Sezary syndrome
  • recurrent mycosis fungoides/Sezary syndrome
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • adult grade III lymphomatoid granulomatosis
  • intraocular lymphoma
  • post-transplant lymphoproliferative disorder
  • refractory multiple myeloma
  • stage IV adult Hodgkin lymphoma
  • recurrent adult Hodgkin lymphoma
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • Waldenstrom macroglobulinemia
  • stage IV adult Burkitt lymphoma
  • recurrent adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent small lymphocytic lymphoma
  • adult nasal type extranodal NK/T-cell lymphoma
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • de novo myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • secondary myelofibrosis
  • AIDS-related peripheral/systemic lymphoma
  • AIDS-related primary CNS lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • stage III multiple myeloma
  • primary systemic amyloidosis
  • extramedullary plasmacytoma
  • monoclonal gammopathy of undetermined significance
  • isolated plasmacytoma of bone
  • Primary Myelofibrosis
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Nervous System Neoplasms
  • Precancerous Conditions
  • Lymphoma, Large-Cell, Immunoblastic
  • Central Nervous System Neoplasms
  • Meningeal Carcinomatosis

Name

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611