Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

Northwestern University

Status and phase

Completed

Early Phase 1

Conditions

Metastatic Cancer

Multiple Myeloma and Plasma Cell Neoplasm

Brain and Central Nervous System Tumors

Unspecified Adult Solid Tumor, Protocol Specific

Secondary Myelofibrosis

Lymphoproliferative Disorder

Precancerous Condition

Chronic Myeloproliferative Disorders

Lymphoma

Leukemia

Myelodysplastic Syndromes

Treatments

Drug: Pemetrexed

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00424242

STU00004482 (Other Identifier)

NU 06C2

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 estimated patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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