Brain Tumors, Central Nervous System Tumors, Leptomeningeal Metastases
Conditions
Keywords
leptomeningeal metastases, temozolomide
Brief summary
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
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.
Interventions
DRUGtemozolomide
Sponsors
National Cancer Institute (NCI)
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | Every 6 weeks | Response will be assessed clinically, cytologically, and radiographically. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics | Every 6 weeks | Drug levels in cerebrospinal fluid assessed every 6 weeks |
| Survival | every 6 weeks | — |
| Quality of Life | Baseline, weekly during cycle 1, before each additional cycle | FACT-Br |
Countries
United States
Outcome results
None listed