Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

1. 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.
2. Determine adverse events related to this regimen in this patient population.
3. Measure temozolomide concentrations in CSF and serum and correlate with appropriate pharmacodynamic parameters (e.g., response) in these patients.

Entry Criteria

Disease Characteristics:

• Documented leptomeningeal metastases
  • Carcinomatous meningitis that is previously untreated or failed prior therapy

    OR

  • Lymphomatous meningitis
    • Newly diagnosed lymphoma (meningeal plus other sites at initial diagnosis) not allowed
    • Must meet 1 of the following criteria:
      • Relapsed after prior standard therapy for leptomeningeal metastases
      • Untreated lymphomatous meningitis eligible if one of the following are true:
        • Over 60 years of age
        • Not likely to have significant potential for cure of systemic disease (i.e., less than 30% 5-year survival estimate)
• Leptomeningeal metastases diagnosed by at least 1 of the following:
  • Positive CSF cytology
  • Negative CSF cytology with compatible clinical syndrome plus MRI and/or CSF abnormalities
    • MRI compatible with leptomeningeal metastases to show abnormal FLAIR sequence signal in the subarachnoid space plus evidence of pial, arachnoid, or dural enhancement after administration of motexafin gadolinium in the absence of clinical findings to suggest infectious meningitis
• Systemic disease that is responding or stable on current therapy not eligible if discontinuing therapy would be deleterious

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• Prior neuroaxis chemotherapy (lumbar puncture, reservoir, or systemic) allowed
• No other concurrent chemotherapy for other sites of disease

Endocrine therapy:

• Not specified

Radiotherapy:

• 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

Surgery:

• Not specified

Other:

• Recovered from any prior recent therapy

Patient Characteristics:

Age:

• See Disease Characteristics
• Over 18

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 6 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No congestive heart failure
• No unstable angina

Other:

• 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

Expected Enrollment

A total of 14-24 patients will be accrued for this study.

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.

Davis TH, Fadul CE, Glantz MJ, et al.: Pilot phase II trial of temozolomide for leptomeningeal metastases: preliminary report. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-460, 2003.

Trial Contact Information

Trial Lead Organizations

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Thomas Davis, MD, Protocol chair		Ph: 603-650-8626; 800-639-6918

Registry Information
Official Title		A Pilot Phase II Trial of Temozolomide in Leptomeningeal Metastases
Trial Start Date		2000-01-03
Registered in ClinicalTrials.gov		NCT00005812
Date Submitted to PDQ		2000-03-24
Information Last Verified		2003-11-20
NCI Grant/Contract Number		CA23108

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