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Temozolomide in Treating Patients With Recurrent High-Grade 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.
 
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

Tracking Information
First Submitted Date  ICMJE February 19, 2008
First Posted Date  ICMJE February 20, 2008
Results First Submitted Date  ICMJE June 17, 2013
Results First Posted Date  ICMJE October 29, 2013
Last Update Posted Date January 31, 2018
Study Start Date  ICMJE October 2007
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: February 19, 2008)
Efficacy, as measured by 6-month progression-free survival, of the dose-intense temozolomide treatment schedule
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2018)
  • 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.
  • Overall Survival [ Time Frame: 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.
  • Patients Progressing After Two First-line Adjuvant Courses of Temozolomide [ Time Frame: 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 ]
  • Patients Progressing 6 Months After Temozolomide is Voluntarily Discontinued [ Time Frame: From beginning of voluntarily temozolomide discontinued up to 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2008)
  • Toxicity Associated With the Dose-intense Temozolomide Treatment Schedule as Assessed by NCI CTCAE v3.0
  • Overall survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Temozolomide in Treating Patients With Recurrent High-Grade Glioma
Official Title  ICMJE Phase II Study of 7 Days On/7 Days Off Temozolomide in Patients With High-Grade Glioma
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Central Nervous System Neoplasm
Intervention  ICMJE Drug: temozolomide
single arm study
Other Name: temodar
Study Arms  ICMJE 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
Intervention: Drug: temozolomide
Publications * Han SJ, Rolston JD, Molinaro AM, Clarke JL, Prados MD, Chang SM, Berger MS, DeSilva A, Butowski NA. Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. Neuro Oncol. 2014 Sep;16(9):1255-62. doi: 10.1093/neuonc/nou044. Epub 2014 Mar 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 19, 2008)
60
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2012
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00619112
Other Study ID Numbers  ICMJE UCSF-07107
SPRI-UCSF-H44867-31182-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Nicholas A. Butowski, MD University of California, San Francisco
Principal Investigator: Susan M. Chang, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP