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

Primary Purpose

Brain Tumors, Central Nervous System Tumors, Leptomeningeal Metastases

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
temozolomide
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Tumors focused on measuring leptomeningeal metastases, temozolomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Norris Cotton Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide

Arm 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.

Outcomes

Primary Outcome Measures

Objective Response
Response will be assessed clinically, cytologically, and radiographically.

Secondary Outcome Measures

Pharmacokinetics
Drug levels in cerebrospinal fluid assessed every 6 weeks
Survival
Quality of Life
FACT-Br

Full Information

First Posted
June 2, 2000
Last Updated
May 13, 2013
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005812
Brief Title
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

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Why Stopped
No objective response documented, protocol terminated after 12 patients.
Study Start Date
January 2000 (undefined)
Primary Completion Date
May 2004 (Actual)
Study Completion Date
May 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Tumors, Central Nervous System Tumors, Leptomeningeal Metastases
Keywords
leptomeningeal metastases, temozolomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
temozolomide
Primary Outcome Measure Information:
Title
Objective Response
Description
Response will be assessed clinically, cytologically, and radiographically.
Time Frame
Every 6 weeks
Secondary Outcome Measure Information:
Title
Pharmacokinetics
Description
Drug levels in cerebrospinal fluid assessed every 6 weeks
Time Frame
Every 6 weeks
Title
Survival
Time Frame
every 6 weeks
Title
Quality of Life
Description
FACT-Br
Time Frame
Baseline, weekly during cycle 1, before each additional cycle

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas H. Davis, MD
Organizational Affiliation
Norris Cotton Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Norris Cotton Cancer Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0002
Country
United States

12. IPD Sharing Statement

Citations:
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
Results Reference
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Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma

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