Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424242
• Other study ID #: NU 06C2
• Secondary ID: STU00004482
• Status: Completed
• Phase: Early Phase 1
• Start date: January 2007
• Est. completion date: September 2011

Study information

• Verified date: September 2021
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Chronic Myeloproliferative Disorders
• Disease
• Leukemia
• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders
• Metastatic Cancer
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Plasma Cell
• Nervous System Neoplasms
• Precancerous Condition
• Precancerous Conditions
• Preleukemia
• Primary Myelofibrosis
• Secondary Myelofibrosis
• Syndrome
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• Pemetrexed
Orally beginning at 500 mg/m2 every 3 weeks until disease progression

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium	Patients will have CSF collected approximately every 6 weeks for assessment while on study.	Every 6 weeks for assessment while on study.
Primary	To determine whether there is any anti-tumor activity against LM with Pemetrexed.	Patients will have a scan every six weeks to assess tumor response.	Every six weeks.
Primary	To determine the safety of Pemetrexed in patients with LM.	Adverse events will be collected every six weeks during patient visits.	After every 2 doses approximately 6 weeks
Primary	To assess the role of serum biomarkers in patients with LM.	Patients will have a one time blood draw to look at serum biomarkers prior to dose one.	Prior to dose one