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Temozolomide in Treating Patients With Recurrent High-Grade Glioma

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ClinicalTrials.gov Identifier: NCT00619112
Recruitment Status : Completed
First Posted : February 20, 2008
Results First Posted : October 29, 2013
Last Update Posted : January 31, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:

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 or disease Intervention/treatment Phase
Recurrent Central Nervous System Neoplasm Drug: temozolomide Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of 7 Days On/7 Days Off Temozolomide in Patients With High-Grade Glioma
Study Start Date : October 2007
Actual Primary Completion Date : December 2011
Actual Study Completion Date : September 2012


Arm Intervention/treatment
Experimental: Temozolomide
single arm trial; Patients treated with temozolomide at a dose of 150mg/m2 daily for seven consecutive days of every other week. One 28-day cycle will include treatment with temozolomide on days 1-7 and days 15-21 with no treatment on days 8-14
Drug: temozolomide
single arm study
Other Name: temodar




Primary Outcome Measures :
  1. 6 Month Progression-free Survival [ Time Frame: First day of treatment until progression or until 6 months mark ]
    Efficacy of dose-intense temozolomide treatment schedule, as measured by 6 months progression-free survival


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) Based on Tumor MGMT (O(6)-Methylguanine-DNA Methyltransferase) Promoter Methylation Status. [ Time Frame: First day of treatment until progression or until 6 months mark ]
    Progression-free survival data (obtained for Primary Outcome Measure) was correlated with tumor MGMT (O(6)-methylguanine-DNA methyltransferase) promoter methylation status, obtained from patients as part of the study.

  2. Overall Survival [ Time Frame: up to 2 years after treatment ]
  3. Patients With Tumors With Functional Alterations of the Mismatch Repair (MMR) System [ Time Frame: prior to start of study ]
    PCR analysis of tumor tissue for microsatellite instability (MSI). Tissue was obtained during surgeries prior this study.

  4. Patients Progressing After Two First-line Adjuvant Courses of Temozolomide [ Time Frame: After two first-line adjuvant courses of temozolomide ]
  5. Patients Progressing Within 6 Months After 6th Adjuvant Course of Temozolomide [ Time Frame: Within 6 months after 6th adjuvant course of temozolomide ]
  6. Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued [ Time Frame: From beginning of voluntarily temozolomide discontinued up to 6 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients with radiographically proven recurrent, intracranial malignant glioma will be eligible for this protocol.
  • All patients must sign an informed consent
  • Patients must have had external beam radiation; there is no limit to the number of prior chemotherapies used.
  • Patients must be > 18 years old, and with a life expectancy > 8 weeks.
  • Patients must have a Karnofsky performance status of > 60.
  • At the time of registration: Patients must have recovered from the toxic effects of prior therapy:
  • Patients must have adequate bone marrow function.
  • Patients must have shown unequivocal radiographic evidence for tumor progression by MRI
  • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: They have recovered from the effects of surgery. Residual disease following resection of recurrent intracranial malignant glioma is not mandated for eligibility into the study.
  • Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry.
  • Patients with prior therapy that included interstitial brachytherapy, stereotactic radiosurgery, or Gliadel wafers must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or MR spectroscopy or surgical documentation of disease.
  • Male and female patients with reproductive potential must use an approved contraceptive method

Exclusion Criteria

  • Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
  • Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
  • Patients must not have active infection or serious intercurrent medical illness.
  • Patients must not be pregnant/breast feeding and must agree to practice adequate contraception.

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 ClinicalTrials.gov identifier (NCT number): NCT00619112


Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Investigators
Principal Investigator: Nicholas A. Butowski, MD University of California, San Francisco
Principal Investigator: Susan M. Chang, MD University of California, San Francisco

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00619112     History of Changes
Obsolete Identifiers: NCT00539552
Other Study ID Numbers: UCSF-07107
SPRI-UCSF-H44867-31182-01
First Posted: February 20, 2008    Key Record Dates
Results First Posted: October 29, 2013
Last Update Posted: January 31, 2018
Last Verified: January 2018

Keywords provided by University of California, San Francisco:
adult glioblastoma
adult gliosarcoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
recurrent adult brain tumor

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents