Gefitinib (Iressa) and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00042991
First received: August 5, 2002
Last updated: June 13, 2011
Last verified: June 2011
Results First Received: February 9, 2011  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Brain and Central Nervous System Tumors
Interventions: Drug: Gefitinib
Radiation: Local Irradiation

  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
Accrual to this study started with the first patient who enrolled on 07/01/2002 and ended with the last patient who enrolled on 05/31/2006. Nine institutions enrolled patients on the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There was no randomization to the three strata, which were distinct based on diagnosis and the use of enzyme inducing anti-convulsants (EIACD).

Reporting Groups
  Description
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed brain stem glioma who were treated at Dose 100 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed brain stem glioma who were treated at Dose 250 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed brain stem glioma who were treated at Dose 375 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 250 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 375 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.

Participant Flow:   Overall Study
    Stratum 1A-100 mg/m^2 of Gefitinib + Radiation     Stratum 1A-250 mg/m^2 of Gefitinib + Radiation     Stratum 1A-375 mg/m^2 of Gefitinib + Radiation     Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation     Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation     Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation     Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD  
STARTED     6     43 [1]   7     2     3     5     3  
Phase-I Trial     6     7 [2]   7     2     3     5     3  
Phase-II Trial     0     36     0     0     0     0     0  
COMPLETED     0     3     1     0     0     0     1  
NOT COMPLETED     6     40     6     2     3     5     2  
Adverse Event                 1                 4                 2                 0                 0                 1                 0  
Withdrawal by Subject                 0                 7                 2                 0                 1                 0                 0  
Disease Progression                 5                 29                 2                 2                 1                 4                 2  
Alternative Therapy                 0                 0                 0                 0                 1                 0                 0  
[1] These 43 patients form the Phase-II cohort, seven contributing from the Phase-I trial.
[2] These seven patients contributed to both Phase-I and Phase-II objectives.



  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.
No text entered.

Reporting Groups
  Description
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed brain stem glioma who were treated at Dose 100 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed brain stem glioma who were treated at Dose 250 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed brain stem glioma who were treated at Dose 375 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 250 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 375 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
Total Total of all reporting groups

Baseline Measures
    Stratum 1A-100 mg/m^2 of Gefitinib + Radiation     Stratum 1A-250 mg/m^2 of Gefitinib + Radiation     Stratum 1A-375 mg/m^2 of Gefitinib + Radiation     Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation     Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation     Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation     Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD     Total  
Number of Participants  
[units: participants]
  6     43     7     2     3     5     3     69  
Age  
[units: participants]
               
<=18 years     6     43     7     2     2     5     3     68  
Between 18 and 65 years     0     0     0     0     1     0     0     1  
>=65 years     0     0     0     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  7.25  ± 2.92     8.02  ± 3.87     10.07  ± 4.71     9.17  ± 8.56     15.91  ± 5.61     11.69  ± 5.40     12.82  ± 2.37     9.01  ± 4.47  
Gender  
[units: participants]
               
Female     3     29     4     0     0     2     2     40  
Male     3     14     3     2     3     3     1     29  
Region of Enrollment  
[units: participants]
               
United States     6     43     7     2     3     5     3     69  



  Outcome Measures
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1.  Primary:   Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy   [ Time Frame: Day 1 of gefitinib therapy to end of week 8 ]

2.  Primary:   Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas   [ Time Frame: Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks ]
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Measure Type Primary
Measure Title Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas
Measure Description Progression-free survival is defined as the interval from intiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurlogical status) or death for patients who failed or to the last date of follow-up for patients without failure
Time Frame Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks  
Safety Issue No  

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.
Here, we only report the results for Phase-II trial as this objective was specifically for the Phase-II trial. This cohort includes seven patients who were treated during Phase-I at Dose 250 mg/m^2 of Gefitinib.

Reporting Groups
  Description
Stratum 1A-Dose 250 mg/m^2 of Gefitinib+Radiation This analysis includes patients with newly diagnosed Brain Stem Glioma patients who received Dose 250 mg/m^2 of Gefitinib+Radiation.

Measured Values
    Stratum 1A-Dose 250 mg/m^2 of Gefitinib+Radiation  
Number of Participants Analyzed  
[units: participants]
  43  
Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas  
[units: Months]
Median ( Full Range )
  7.43  
  ( 1.25 to 37.95 )  

No statistical analysis provided for Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas



3.  Primary:   Median Survival in Newly Diagnosed Brain Stem Gliomas   [ Time Frame: Assessed from the start of therapy until three years after initiation of gefitinib therapy ]

4.  Secondary:   Change in Tumor Volume Measured on Fluid Attenuated Inversion Recovery (FLAIR) Imaging at Before the Protocol Therapy Started and at Two Weeks After Completion of Radiation   [ Time Frame: Baseline and two weeks post completion of radiation ]

5.  Secondary:   Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation   [ Time Frame: Baseline and two weeks post completion of radiation ]

6.  Secondary:   Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation   [ Time Frame: Baseline and two weeks post completion of radiation ]

7.  Secondary:   Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation   [ Time Frame: Baseline and two weeks post completion of radiation ]

8.  Secondary:   Mean Tumor to Gray Matter Ratio Measured at Baseline   [ Time Frame: Baseline ]

9.  Secondary:   Mean Tumor to White Matter Ratio Measured at Baseline   [ Time Frame: Baseline ]

10.  Secondary:   Peak Serum Concentration of Gefitinib (Cmax)   [ Time Frame: Week 2 of course 1 ]

11.  Secondary:   Elimination Half Life of Gefitinib (t1/2)   [ Time Frame: Week 2 of course 1 ]

12.  Secondary:   Clearance of Gefitinib (Cl)   [ Time Frame: Week 2 of course 1 ]

13.  Secondary:   Time of Maximum Clearance of Gefitinib (Tmax)   [ Time Frame: Week 2 of course 1 ]

14.  Secondary:   Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC)   [ Time Frame: Week 2 of course 1 ]

15.  Secondary:   Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification   [ Time Frame: Pre-treatment ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Mehmet Kocak
Organization: Operations and Biostatistics Center for Pediatric Brain Tumor Consortium (PBTC)
phone: 9015952947
e-mail: mehmet.kocak@stjude.org


No publications provided


Responsible Party: James M. Boyett, Executive Director Operations and Biostatistics Center for the PBTC, Pediatric Brain Tumor Consortium (PBTC)
ClinicalTrials.gov Identifier: NCT00042991     History of Changes
Other Study ID Numbers: CDR0000069490, PBTC-007, 715055
Study First Received: August 5, 2002
Results First Received: February 9, 2011
Last Updated: June 13, 2011
Health Authority: United States: Food and Drug Administration