Radiation Therapy (RT) and Temozolomide (TMZ) in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00304031
First received: March 15, 2006
Last updated: March 28, 2014
Last verified: March 2014
Results First Received: March 28, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Brain and Central Nervous System Tumors
Interventions: Drug: Concurrent temozolomide
Radiation: Concurrent radiation therapy
Drug: 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle
Drug: 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
No Adjuvant TMZ (Not Randomized) Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm.
Conventional Adjuvant TMZ Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Dose-dense Adjuvant TMZ Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.

Participant Flow for 3 periods

Period 1:   Registration
    No Adjuvant TMZ (Not Randomized)     Conventional Adjuvant TMZ     Dose-dense Adjuvant TMZ  
STARTED     1173 [1]   0 [2]   0 [2]
COMPLETED     1125 [3]   0     0  
NOT COMPLETED     48     0     0  
Ineligible                 48                 0                 0  
[1] All patients were registered to concomitant treatment; randomized after completing this treatment.
[2] Patients were not randomized to adjuvant TMZ until after completion of concomitant treatment.
[3] Patients determined to be ineligible after registration were excluded.

Period 2:   Concomitant Radiation Therapy and TMZ
    No Adjuvant TMZ (Not Randomized)     Conventional Adjuvant TMZ     Dose-dense Adjuvant TMZ  
STARTED     1125 [1]   0 [2]   0 [2]
COMPLETED     833 [3]   0     0  
NOT COMPLETED     292     0     0  
Ineligible due to insufficient tissue                 144                 0                 0  
Disease progression                 48                 0                 0  
Patient refusal                 19                 0                 0  
Death                 18                 0                 0  
Physician preference                 15                 0                 0  
Toxicity                 10                 0                 0  
Other complicating disease                 1                 0                 0  
Other, not otherwise specified                 37                 0                 0  
[1] All patients were registered to concomitant treatment; randomized after completing this treatment.
[2] Patients were not randomized to adjuvant TMZ until after completion of concomitant treatment.
[3] These patients successfully completed concomitant treatment and met requirements for randomization.

Period 3:   Randomization to Adjuvant TMZ Arm
    No Adjuvant TMZ (Not Randomized)     Conventional Adjuvant TMZ     Dose-dense Adjuvant TMZ  
STARTED     0 [1]   411 [1]   422 [1]
COMPLETED     0     411 [2]   420 [3]
NOT COMPLETED     0     0     2  
No follow-up collected                 0                 0                 2  
[1] Patients who met requirements were randomized to an adjuvant TMZ arm after concomitant treatment.
[2] Subjects contributing data to the primary analysis are considered to have completed the study.
[3] Subjects contributing data to the primary analysis are considered to have completed the study



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients who were randomized.

Reporting Groups
  Description
No Adjuvant TMZ (Not Randomized ) Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm.
Conventional Adjuvant TMZ Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Dose-dense Adjuvant TMZ Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Total Total of all reporting groups

Baseline Measures
    No Adjuvant TMZ (Not Randomized )     Conventional Adjuvant TMZ     Dose-dense Adjuvant TMZ     Total  
Number of Participants  
[units: participants]
  292     411     422     1125  
Age  
[units: years]
Median ( Full Range )
  60.5  
  ( 22 to 87 )  
  57  
  ( 22 to 84 )  
  58  
  ( 21 to 84 )  
  58  
  ( 21 to 87 )  
Gender  
[units: participants]
       
Female     126     172     185     483  
Male     166     239     237     642  



  Outcome Measures

1.  Primary:   Overall Survival (OS)   [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after 647 deaths have been reported. ]

2.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs after 647 deaths have been reported. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

3.  Secondary:   Comparison of OS and PFS in Patients With Unmethylated MGMT   [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs after 647 deaths have been reported. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Comparison of OS and PFS in Patients With Methylated MGMT   [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs after 647 deaths have been reported. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Correlation of Tumor MGMT Gene Methylation Status With Treatment Response   [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs after 647 deaths have been reported. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

6.  Secondary:   Toxicity   [ Time Frame: From start of treatment to end of follow-up ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

7.  Secondary:   Correlation of PFS With OS at 6 Months   [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs after 647 deaths have been reported. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This was a two-stage study in which participants were registered, received concomitant RT and TMZ, and then were randomized to standard or dose-dense adjuvant TMZ. Some patients were not randomized, resulting in the third arm (No adjuvant TMZ).


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Wendy Seiferheld
Organization: Radiation Therapy Oncology Group (RTOG)
e-mail: wseiferheld@acr.org


Publications of Results:
Armstrong TS, Wefel JS, Wang M, et al.: Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525. [Abstract] J Clin Oncol 29 (Suppl 15): A-2016, 2011.
Wang M, Dignam J, Won M, et al.: Variation over time and interdependence between disease progression and death among patients with glioblastoma (GBM) on RTOG 0525. [Abstract] J Clin Oncol 29 (Suppl 15): A-2017, 2011.
Aldape KD, Jones G, Wang M, et al.: MGMT methylation testing in RTOG 0525: A phase III trial of newly diagnosed glioblastoma. [Abstract] J Clin Oncol 27 (Suppl 15): A-2051, 2009.

Publications automatically indexed to this study:

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00304031     History of Changes
Other Study ID Numbers: RTOG-0525, CDR0000465183, EORTC-26052, EORTC-22053, NCI-2009-00731
Study First Received: March 15, 2006
Results First Received: March 28, 2014
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration