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

A Pilot Phase II Trial of Temozolomide in Leptomeningeal Metastases

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.

Study Overview

• Status: Terminated
• Conditions: Brain Tumors; Central Nervous System Tumors; Leptomeningeal Metastases
• Intervention / Treatment: Drug: temozolomide

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Temozolomide; 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.	Drug: temozolomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response	Response will be assessed clinically, cytologically, and radiographically.	Every 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Drug levels in cerebrospinal fluid assessed every 6 weeks	Every 6 weeks
Survival		every 6 weeks
Quality of Life	FACT-Br	Baseline, weekly during cycle 1, before each additional cycle

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Thomas H. Davis, MD, Norris Cotton Cancer Center

Publications and helpful links

General Publications

• 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

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): May 1, 2004
• Study Completion (Actual): May 1, 2004

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 14, 2013
• Last Update Submitted That Met QC Criteria: May 13, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: temozolomide; leptomeningeal metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms by Site; Neoplastic Processes; Meningeal Neoplasms; Neoplasms; Neoplasm Metastasis; Nervous System Neoplasms; Central Nervous System Neoplasms; Meningeal Carcinomatosis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: D9812; DMS-9812; NCI-G00-1782