Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have leptomeningeal metastases from a solid tumor or lymphoma.

Detailed Description
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OBJECTIVES: Determine the objective response rate, survival time, and quality of life of patients with leptomeningeal metastases from a solid tumor or lymphoma when treated with oral temozolomide. Determine adverse events related to this regimen in this patient population. Measure temozolomide concentrations in CSF and serum and correlate with appropriate pharmacodynamic parameters (e.g., response) in these patients. OUTLINE: Patients receive oral temozolomide daily for 6 weeks. Courses repeat every 10 weeks in the absence of unacceptable toxicity or disease progression. Patients with a complete response (CR) receive 2 additional courses after achieving CR. Patients with a CR except for residual radiographic abnormalities that persist unchanged for 2 full courses continue for 4 courses past best response. Quality of life is assessed at baseline, weekly for the first 4 weeks of therapy, and then monthly thereafter. PROJECTED ACCRUAL: A total of 14-24 patients will be accrued for this study.

Official Title
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A Pilot Phase II Trial of Temozolomide in Leptomeningeal Metastases

Conditions
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Brain Tumors, Central Nervous System Tumors, Leptomeningeal Metastases

Intervention / Treatment
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* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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Documented leptomeningeal metastases Carcinomatous meningitis that is previously untreated or failed prior therapy OR Lymphomatous meningitis Systemic disease that is responding or stable on current therapy not eligible if discontinuing therapy would be deleterious Age 18 and over Karnofsky Performance Status 60-100% Life expectancy of at least 6 weeks Absolute neutrophil count greater than 1,500/μL Platelet count greater than 100,000/μL Creatinine no greater than 2.0 mg/dL No congestive heart failure No unstable angina Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No contraindication to diagnostic sampling of CSF via lumbar puncture or reservoir No medical conditions that would interfere with absorption of oral medication (e.g., malabsorption, obstruction, or frequent vomiting) No uncontrolled infection Prior neuroaxis chemotherapy (lumbar puncture, reservoir, or systemic) allowed No other concurrent chemotherapy for other sites of disease No prior radiotherapy to areas of measurable meningeal disease unless there is clear radiographic progression in these areas No prior radiotherapy to greater than 30% of bone marrow Prior radiotherapy to the neuroaxis allowed No concurrent radiotherapy for other sites of disease or for progressive disease Recovered from any prior recent therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide<br>Oral temozolomide 75 mg/m2/day for 6 weeks, followed by 4 week break. Cycles will continue until: disease progression intolerable toxicity complete response - 2 full additional cycles if response is complete except for residual radiographic abnormalities that persist unchanged for 2 full cycles: continue for 4 cycles past best response. | Drug: temozolomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response | Response will be assessed clinically, cytologically, and radiographically. | Every 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Drug levels in cerebrospinal fluid assessed every 6 weeks | Every 6 weeks | 
| Survival |  | every 6 weeks | 
| Quality of Life | FACT-Br | Baseline, weekly during cycle 1, before each additional cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leptomeningeal metastases, temozolomide