Temozolomide in Treating Patients With Recurrent High-Grade Glioma

Temozolomide in Treating Patients With Recurrent High-Grade Glioma
The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).   Recruitment status was  Recruiting

First Received on February 19, 2008.  
Last Updated on July 7, 2009  
History of Changes
Sponsor: University of California, San Francisco
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00619112

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with recurrent high-grade glioma.

Condition Intervention Phase
Brain and Central Nervous System Tumors Drug: temozolomide
Genetic: DNA methylation analysis
Genetic: microsatellite instability analysis
Genetic: polymerase chain reaction
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of 7 Days On/7 Days Off Temozolomide in Patients With High-Grade Glioma

Resource links provided by NLM:

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

Primary Outcome Measures:

  • Efficacy, as measured by 6-month progression-free survival, of the dose-intense temozolomide treatment schedule [ Designated as safety issue: No ]

Secondary Outcome Measures:

  • Toxicity associated with the dose-intense temozolomide treatment schedule as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2007
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

Detailed Description:



  • Determine the efficacy, as measured by 6-month progression-free survival, of a dose-intense temozolomide treatment schedule in patients with recurrent high-grade glioma.


  • Assess the toxicities of this dose-intense temozolomide.
  • Determine the overall survival of patients treated with this dose-intense schedule.
  • Determine whether methylation status of the MGMT gene within patients’ tumors predicts greater efficacy (progression-free survival), in patients treated on this protocol.
  • Determine whether patients’ tumors have functional alterations of the mismatch repair (MMR) system by PCR analysis for microsatellite instability (MSI) and whether such alterations may influence outcome in patients treated on this protocol.
  • Determine how initial success with temozolomide may influence outcome in recurrent patients treated on this protocol by evaluating patients progressing after two first-line adjuvant courses of temozolomide, patients progressing within 6 months after the 6th adjuvant course of temozolomide, and patients progressing 6 months after temozolomide is voluntarily discontinued.

OUTLINE: Patients receive oral temozolomide once daily on days 1-7 and days 15-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded tissue blocks or unstained paraffin slides from available surgical samples are evaluated for molecular abnormalities in the tumor, including (but not limited to) MGMT status and microsatellite instability.

After completion of study therapy, patients are followed every 3 months for survival.

PROJECTED ACCRUAL: A total of 40 patients with WHO II grade 4 tumors (glioblastoma multiforme [GBM]) and 20 patients with WHO II grade 3 tumors (non-GBM) will be accrued for this study.


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


  • Radiographically proven recurrent intracranial malignant glioma, including any of the following subtypes:

    • Glioblastoma multiforme
    • Gliosarcoma
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Anaplastic mixed oligoastrocytoma
    • Malignant astrocytoma not otherwise specified
  • Original histological diagnosis of low-grade glioma with subsequent histological diagnosis of malignant glioma allowed
  • Must show unequivocal radiographic evidence of tumor progression by MRI or CT scan while on a stable dose of steroids for ≥ 5 days

    • A new baseline MRI or CT scan is required if the steroid dose is increased between the date of imaging and the date of registration
  • Must have received prior treatment with ≥ 1 course of standard adjuvant 5-day dose schedule of temozolomide

    • May have had tumor progression while on 5 -day temozolomide schedule or while on another agent
  • Failed prior external-beam radiotherapy
  • Confirmation of true progressive disease (not radiation necrosis) by PET, thallium scanning, MR spectroscopy, or surgical documentation required if patient received prior interstitial brachytherapy or stereotactic radiosurgery
  • Patients having undergone recent resection of recurrent or progressive tumor are eligible provided all of the following conditions apply:

    • Recovered from surgery
    • Residual disease following resection of recurrent intracranial malignant glioma is not mandated for eligibility into the study


  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • WBC ≥ 3,000/µL
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • SGOT < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • Creatinine < 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after discontinuation of study treatment
  • No significant medical illness that cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy, in the investigator’s opinion
  • No other cancer except nonmelanoma skin cancer or carcinoma in situ of the cervix unless patient is in complete remission and off all therapy for that disease for at least 3 years
  • No active infection or serious intercurrent medical illness
  • No other disease that will obscure toxicity or dangerously alter drug metabolism


  • No limitation to the number of prior treatment
  • Recovered from prior therapy
  • At least 42 days since prior radiotherapy
  • At least 28 days since prior cytotoxic therapy (42 days for nitrosoureas)
  • At least 28 days since investigational agent
  • At least 21 days since prior procarbazine
  • At least 14 days since prior vincristine
  • At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin), except radiosensitizers
  • Concurrent neurosurgical management allowed if not for tumor progression
  • No prior Gliadel wafers at time of original resection
  • No concurrent prophylactic filgrastim (G-CSF)
  • No other concurrent investigational agent
  • No other concurrent anticancer therapy (i.e., chemotherapy, radiotherapy, hormonal treatment, or immunotherapy)
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619112

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office – UCSF Helen Diller Family Comprehensi     877-827-3222        
Sponsors and Collaborators
University of California, San Francisco
Principal Investigator: Nicholas A. Butowski, MD University of California, San Francisco
Principal Investigator: Susan M. Chang, MD University of California, San Francisco
  More Information

Additional Information:

No publications provided

ClinicalTrials.gov Identifier: NCT00619112    
History of Changes
Obsolete Identifiers: NCT00539552
Other Study ID Numbers: CDR0000572434, UCSF-H44867-31182-01, UCSF-07107, SPRI-UCSF-H44867-31182-01
Study First Received: February 19, 2008
Last Updated: July 7, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):

adult glioblastoma
adult gliosarcoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
recurrent adult brain tumor

Additional relevant MeSH terms:

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
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2012

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