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Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006025
First received: July 5, 2000
Last updated: November 22, 2008
Last verified: August 2004
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: irinotecan hydrochloride
Drug: temozolomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients With Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: November 2000
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • 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

Hepatic:

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

Renal:

  • Creatinine no greater than 1.5 mg/dL

Cardiovascular:

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

Other:

  • 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

PRIOR CONCURRENT THERAPY:

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

Chemotherapy:

  • 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

Radiotherapy:

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

Surgery:

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

Other:

  • 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
  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: NCT00006025

Locations
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
North American Brain Tumor Consortium
Investigators
Study Chair: Wai-Kwan A. Yung, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00006025     History of Changes
Other Study ID Numbers: CDR0000068037, NABTC-9907, UCLA-0006095
Study First Received: July 5, 2000
Last Updated: November 22, 2008
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Irinotecan
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014