Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

NCT ID: NCT00424242

Last Updated: 2021-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2011-09-30

Brief 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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Escalating doses of Pemetrexed

Escalating doses of Pemetrexed beginning at 500 mg/m2

Group Type: EXPERIMENTAL

Pemetrexed

Intervention Type: DRUG

Orally beginning at 500 mg/m2 every 3 weeks until disease progression

Interventions

Pemetrexed

Orally beginning at 500 mg/m2 every 3 weeks until disease progression

Intervention Type: DRUG

Other Intervention Names

Alimta; LY231514

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey J. Raizer, MD

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

STU00004482

Identifier Type: OTHER

Identifier Source: secondary_id

NU 06C2

Identifier Type: -

Identifier Source: org_study_id