Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases - Full Text View

Sponsor:	Northwestern University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00424242

Purpose

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 Leukemia Lymphoma Lymphoproliferative Disorder Metastatic Cancer Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Precancerous Condition Secondary Myelofibrosis Unspecified Adult Solid Tumor, Protocol Specific	Drug: Pemetrexed	Phase 0

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia essential thrombocythemia familial acute myeloid leukemia with mutated CEBPA hemophilia

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Hodgkin Disease Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes

Drug Information available for: Pemetrexed Pemetrexed disodium

U.S. FDA Resources

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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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 2012
Primary Completion Date:	March 2010 (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 pemetrexed

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424242

Locations

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)

Investigators

Principal Investigator:

Jeffrey J. Raizer, MD

Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Jeffrey Raizer, Northwestern University
ClinicalTrials.gov Identifier:	NCT00424242 History of Changes
Other Study ID Numbers:	NU 06C2, STU00004482
Study First Received:	January 16, 2007
Last Updated:	April 8, 2011
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

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:

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
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders

ClinicalTrials.gov processed this record on May 22, 2012