Clinical trial NCT00005812: Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma
Official title: A Pilot Phase II Trial of Temozolomide in Leptomeningeal Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Brain Tumors
Central Nervous System Tumors
Leptomeningeal Metastases
Keywords: leptomeningeal metastases
temozolomide
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective Response
timeFrame: Every 6 weeks
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: Every 6 weeks
measure: Survival
timeFrame: every 6 weeks
measure: Quality of Life
timeFrame: Baseline, weekly during cycle 1, before each additional cycle
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Thomas H. Davis, MD
role: STUDY_CHAIR
References:
citation: 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. ISBN 1932312021