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

This study has been terminated.
(No objective response documented, protocol terminated after 12 patients.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00005812
First received: June 2, 2000
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Brain Tumors
Central Nervous System Tumors
Leptomeningeal Metastases
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Phase II Trial of Temozolomide in Leptomeningeal Metastases

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Objective Response [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
    Response will be assessed clinically, cytologically, and radiographically.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]
    Drug levels in cerebrospinal fluid assessed every 6 weeks

  • Survival [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: Baseline, weekly during cycle 1, before each additional cycle ] [ Designated as safety issue: No ]
    FACT-Br


Enrollment: 12
Study Start Date: January 2000
Study Completion Date: May 2004
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005812

Locations
United States, New Hampshire
Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756-0002
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Study Chair: Thomas H. Davis, MD Norris Cotton Cancer Center
  More Information

No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00005812     History of Changes
Other Study ID Numbers: D9812, DMS-9812, NCI-G00-1782
Study First Received: June 2, 2000
Last Updated: May 13, 2013
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
leptomeningeal metastases
temozolomide

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Meningeal Carcinomatosis
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Nervous System Neoplasms
Meningeal Neoplasms
Neoplasms by Site
Neoplastic Processes
Nervous System Diseases
Pathologic Processes
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014