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Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006025
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 27, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of temozolomide plus irinotecan in treating patients who have recurrent malignant glioma.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: irinotecan hydrochloride Drug: temozolomide Phase 1

Detailed Description:


  • Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan when administered with temozolomide in patients with recurrent malignant glioma.
  • Determine the safety profile of this regimen in this patient population.
  • Determine the efficacy of this treatment regimen as measured by 6-month progression-free survival and objective tumor response in these patients.
  • Characterize the pharmacokinetics of this treatment regimen in these patients.
  • Determine the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., phenytoin, phenobarbital, carbamazepine, or primidone) (yes vs no).

In phase I of the study, patients receive oral temozolomide on days 1-5 and irinotecan IV over 90 minutes on days 1 and 14. Treatment continues every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients concurrently on EIAEDs undergo dose escalation of irinotecan. Cohorts of 3 to 6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

In phase II of the study, patients receive the same treatment as in phase I at the MTD.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months until progression, and then every 4 months for survival.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for phase I within 10 months and 48 patients will be accrued for phase II within 6-8 months.

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Study Type : Interventional  (Clinical Trial)
Allocation: N/A
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Official Title: Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients With Recurrent Malignant Glioma
Actual Study Start Date : January 5, 2001
Actual Primary Completion Date : January 10, 2005
Actual Study Completion Date : December 1, 2007

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed supratentorial malignant primary glioma of one of the following subtypes:

    • Glioblastoma multiforme
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Mixed malignant glioma
  • Original histology of low-grade glioma allowed if subsequent histological confirmation of malignant glioma
  • Measurable recurrent or residual primary disease by MRI

    • Lesions with clearly defined margins
  • Evidence of tumor recurrence or progression by MRI or CT scan
  • Confirmation of true progressive disease by PET or thallium scan, magnetic resonance spectroscopy, or surgical documentation after prior interstitial brachytherapy or stereotactic radiosurgery
  • No more than 3 relapses after prior chemotherapy/cytotoxic therapy (including polifeprosan 20 with carmustine implant) for phase I and no more than 2 relapses for phase II



  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified


  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 g/dL


  • Bilirubin no greater than 1.5 mg/dL
  • SGOT no greater than 2 times upper limit of normal


  • Creatinine no greater than 1.5 mg/dL


  • No uncontrolled hypertension, unstable angina, or symptomatic congestive heart failure
  • No myocardial infarction within the past 6 months
  • No serious uncontrolled cardiac arrhythmia


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No mental incapacitation
  • HIV negative
  • No AIDS-related disease
  • No significant ongoing alcoholism or substance abuse
  • No severe nonmalignant systemic disease
  • No active infection
  • No other severe disease that would preclude study


Biologic therapy:

  • At least 1 week since prior interferon or thalidomide and recovered
  • No concurrent anticancer immunotherapy
  • No concurrent sargramostim (GM-CSF)
  • No concurrent prophylactic filgrastim (G-CSF) during first course of study therapy


  • See Disease Characteristics
  • Recovered from prior chemotherapy
  • At least 2 weeks since prior vincristine
  • At least 3 weeks since prior procarbazine
  • At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosourea)
  • Prior radiosensitizers allowed
  • No prior temozolomide or irinotecan
  • No other concurrent anticancer chemotherapy

Endocrine therapy:

  • At least 1 week since prior tamoxifen and recovered
  • No concurrent anticancer hormonal therapy
  • Phase II:

    • Non-increasing dose of corticosteroids allowed


  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy and recovered
  • No concurrent anticancer radiotherapy


  • See Disease Characteristics
  • At least 1-3 weeks since prior surgical resection and recovered


  • At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) and recovered
  • Concurrent enzyme-inducing anti-epileptic drugs with or without steroids allowed
  • No concurrent valproic acid as a single agent
  • No concurrent medication that would preclude study (e.g., nonsteroidal immunosuppressive agents)
  • No other concurrent investigational drugs
  • No concurrent participation in other clinical study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006025

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United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
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Study Chair: Wai-Kwan A. Yung, MD M.D. Anderson Cancer Center
Publications of Results:
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00006025    
Other Study ID Numbers: NABTC-9907
CDR0000068037 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2012-02353 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents