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

Dartmouth Health

Status and phase: Terminated; Phase 2

Conditions: Central Nervous System Tumors; Brain Tumors; Leptomeningeal Metastases

Treatments: Drug: temozolomide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005812

D9812

NCI-G00-1782

DMS-9812

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Temozolomide

Experimental group

Description:

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.

Treatment:

Drug: temozolomide