Temozolomide in Treating Patients With Recurrent High-Grade Glioma

January 5, 2018 updated by: University of California, San Francisco

Phase II Study of 7 Days On/7 Days Off Temozolomide in Patients With High-Grade Glioma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
First day of treatment until progression or until 6 months mark

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
First day of treatment until progression or until 6 months mark
Overall Survival
Time Frame: up to 2 years after treatment
up to 2 years after treatment
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.
prior to start of study
Patients Progressing After Two First-line Adjuvant Courses of Temozolomide
Time Frame: After two first-line adjuvant courses of temozolomide
After two first-line adjuvant courses of temozolomide
Patients Progressing Within 6 Months After 6th Adjuvant Course of Temozolomide
Time Frame: Within 6 months after 6th adjuvant course of temozolomide
Within 6 months after 6th adjuvant course of temozolomide
Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued
Time Frame: From beginning of voluntarily temozolomide discontinued up to 6 months
From beginning of voluntarily temozolomide discontinued up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (ACTUAL)

December 1, 2011

Study Completion (ACTUAL)

September 1, 2012

Study Registration Dates

First Submitted

February 19, 2008

First Submitted That Met QC Criteria

February 19, 2008

First Posted (ESTIMATE)

February 20, 2008

Study Record Updates

Last Update Posted (ACTUAL)

January 31, 2018

Last Update Submitted That Met QC Criteria

January 5, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSF-07107
  • SPRI-UCSF-H44867-31182-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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