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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-03022 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| PBTC-007 | Other Identifier | Pediatric Brain Tumor Consortium | |
| PBTC-007 | Other Identifier | CTEP | |
| U01CA081457 | U.S. NIH Grant/Contract | View source |
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Biological therapies such as gefitinib may interfere with the growth of the tumor cells and may make the tumor cells more sensitive to radiation therapy. This phase I/II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma.
PRIMARY OBJECTIVES:
I. To define the safety of gefitinib administered in conjunction with irradiation in children with newly diagnosed non-disseminated diffuse intrinsic brainstem gliomas and newly diagnosed incompletely resected supratentorial malignant gliomas (STMG) not receiving enzyme inducing anticonvulsant drugs (EIACDs).
II. To define the safety of gefitinib in children with newly diagnosed, incompletely resected STMG receiving EIACDs.
III. To assess the safety and efficacy of gefitinib given with radiation therapy in children newly diagnosed with a brainstem glioma as measured by progression-free survival and to estimate the survival distribution.
SECONDARY OBJECTIVES:
I. To compare hemodynamic magnetic resonance (MR) parameters to metabolic fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) scanning and correlate both with clinical response or progression in this population.
II. To characterize the expression of ErbB1 receptors in tissue from STMG patients using immunohistochemistry and western blot assays.
III. To characterize the pharmacokinetics of gefitinib in the above patient groups and determine the effects of EIACD on the pharmacokinetics.
IV. To explore the pharmacogenetic polymorphisms for gefitinib (e.g., CYP3A4/5 and BCRP) and relate them to gefitinib pharmacokinetics and pharmacodynamics (phenotype-genotype).
OUTLINE: This is a multicenter, dose-escalation study of gefitinib (Phase I closed to accrual effective 10/27/2003). Patients are stratified according to the following:
Stratum 1A: Intrinsic brain stem glioma; not receiving concurrent enzyme-inducing anticonvulsant drugs (EIACDs) Stratum 1B: Incompletely resected supratentorial malignant gliomas (STMG); not receiving concurrent EIACDs Stratum 2: Incompletely resected STMG; receiving concurrent EIACDs.
Phase I portion (patients in strata 1A, 1B, and 2) (phase I closed to accrual effective 10/27/2003): Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Phase II portion (patients in stratum 1A): Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed brain stem gliomas (BSG) are treated at the MTD or the recommended Phase-II dose.
Patients are followed for three months after the last protocol treatment for those enrolled strictly on the phase I component. Patients contributing to the phase II portion are followed until the earliest of date of death or three years after initiation of protocol therapy.
PROJECTED ACCRUAL: Considering the seven dose levels to be investigated in three strata, where each dose level can accrue up to six patients, a total of 126 patients (42 for each strata) may be accrued for this study within 2 years. (Phase I closed to accrual effective 10/27/2003). A total of 40 patients including the patients treated at the maximum tolerated dose or the recommended Phase-II dose during Phase I will be accrued for phase II of this study within 10 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (gefitinib and radiation therapy) | Experimental | Phase I portion: Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity. Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| gefitinib | Drug | Given orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy | The dose limiting toxicity (DLT) analysis population consists of stratum 1A phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD based on the tradional 3+3 design, where a dose is considered a safe dose only when 0 out of 3, or at most 1 out of 6 patients has DLTs. When two or more patients in a group of 2 to 6 patients had DLTs, then that dose level was considered to be too toxic. | Day 1 of gefitinib therapy to end of week 8 |
| Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas | 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 | Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks |
| Median Survival in Newly Diagnosed Brain Stem Gliomas | Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients | Assessed from the start of therapy until three years after initiation of gefitinib therapy |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. In this particular objective, the study aimed to investigate how radiation+gefitinib affect the tumor volume. Tumor volume is measured using Fluid Attenuated Inversion Recovery (FLAIR) before and after the radiation therapy. |
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Inclusion Criteria:
Tumor:
Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration
Prior/concurrent therapy:
ANC > 1,000/ul
Platelets > 100,000/ul (transfusion independent)
Hemoglobin > 8g/dl (may be transfused)
Patients may have bone marrow involvement by disease
Creatinine < 2 x normal for age or GFR > 70 ml/min/1.73m^2
Bilirubin < 1.5 x normal institutional normal for age
SGPT (ALT) < 3 x institutional normal for age
Pregnant and/or lactating patients are excluded; patients of childbearing potential should not become pregnant and should not father a child during treatment with gefitinib; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
Signed informed consent according to institutional guidelines must be obtained prior to study entry
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Geyer | Pediatric Brain Tumor Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pediatric Brain Tumor Consortium | Memphis | Tennessee | 38105 | United States |
There was no randomization to the three strata, which were distinct based on diagnosis and the use of enzyme inducing anti-convulsants (EIACD).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Stratum 1A-250 mg/m^2 of Gefitinib + Radiation |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| radiation therapy | Radiation | Undergo standard brain irradiation |
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| pharmacological study | Other | Correlative studies |
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| laboratory biomarker analysis | Other | Correlative studies |
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| Baseline and two weeks post completion of radiation |
| Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Volume enhancing is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. | Baseline and two weeks post completion of radiation |
| Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Diffusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. | Baseline and two weeks post completion of radiation |
| Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Perfusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. | Baseline and two weeks post completion of radiation |
| Mean Tumor to Gray Matter Ratio Measured at Baseline | This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal gray matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to gray matter ratio value and the median of these values across patients is reported. | Baseline |
| Mean Tumor to White Matter Ratio Measured at Baseline | This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal white matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to white matter ratio value and the median of these values across patients is reported. | Baseline |
| Peak Serum Concentration of Gefitinib (Cmax) | Week 2 of course 1 |
| Elimination Half Life of Gefitinib (t1/2) | Week 2 of course 1 |
| Clearance of Gefitinib (Cl) | Week 2 of course 1 |
| Time of Maximum Clearance of Gefitinib (Tmax) | Week 2 of course 1 |
| Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC) | Week 2 of course 1 |
| Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification | Epidermal growth factor receptor (EFGR) is a protein found on the surface of cells to which epidermal growth factor (EGF) binds. When EGF attaches to EGFR, it activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. | Pre-treatment |
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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| Phase-I Trial |
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| Phase-II Trial |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | 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. |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy | The dose limiting toxicity (DLT) analysis population consists of stratum 1A phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD based on the tradional 3+3 design, where a dose is considered a safe dose only when 0 out of 3, or at most 1 out of 6 patients has DLTs. When two or more patients in a group of 2 to 6 patients had DLTs, then that dose level was considered to be too toxic. | This cohort includes only the patients who were enrolled and treated on Gefitinib+Radiation during the Phase I component of the trial, where the safety of Gefitinib was assedded at Dose Levels 100 mg/m^2, 250 mg/m^2, and 375 mg/m^2. | Posted | Number | Participants | Day 1 of gefitinib therapy to end of week 8 |
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| Primary | Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas | 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 | 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. | Posted | Median | Full Range | Months | Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks |
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| Primary | Median Survival in Newly Diagnosed Brain Stem Gliomas | Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients | Posted | Median | Full Range | Months | Assessed from the start of therapy until three years after initiation of gefitinib therapy |
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| 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 | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. In this particular objective, the study aimed to investigate how radiation+gefitinib affect the tumor volume. Tumor volume is measured using Fluid Attenuated Inversion Recovery (FLAIR) before and after the radiation therapy. | Out of 43 patients, 35 patients had brain MRI before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the volumetric data from these 35 patients. | Posted | Median | Full Range | cc | Baseline and two weeks post completion of radiation |
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| Secondary | Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Volume enhancing is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. | Out of 43 patients, for only 19 patients, enhacing tumor was greater than zero based on brain MRI scans before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the enhancing volumetric data from these 19 patients. | Posted | Median | Full Range | cc | Baseline and two weeks post completion of radiation |
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| Secondary | Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Diffusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. | Out of 43 patients, 29 patients had diffusion scans before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the volumetric data from these 29 patients. | Posted | Median | Full Range | Ratio | Baseline and two weeks post completion of radiation |
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| Secondary | Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Perfusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. | Out of 43 patients, 20 patients had perfusion scans before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the volumetric data from these 20 patients. | Posted | Median | Full Range | Ratio | Baseline and two weeks post completion of radiation |
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| Secondary | Mean Tumor to Gray Matter Ratio Measured at Baseline | This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal gray matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to gray matter ratio value and the median of these values across patients is reported. | Out of 43 patients, only 18 Patients had baseline PET scans. Therefore, this analysis is based on these 18 patients. | Posted | Median | Full Range | Ratio | Baseline |
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| Secondary | Mean Tumor to White Matter Ratio Measured at Baseline | This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal white matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to white matter ratio value and the median of these values across patients is reported. | Out of 43 patients, only 18 Patients had baseline PET scans. Therefore, this analysis is based on these 18 patients. | Posted | Median | Full Range | Ratio | Baseline |
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| Secondary | Peak Serum Concentration of Gefitinib (Cmax) | PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication. | Posted | Median | Full Range | mcg/ml | Week 2 of course 1 |
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| Secondary | Elimination Half Life of Gefitinib (t1/2) | PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication. | Posted | Median | Full Range | hour | Week 2 of course 1 |
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| Secondary | Clearance of Gefitinib (Cl) | PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication. | Posted | Median | Full Range | L/hr/m2 | Week 2 of course 1 |
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| Secondary | Time of Maximum Clearance of Gefitinib (Tmax) | PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication. | Posted | Median | Full Range | Hour | Week 2 of course 1 |
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| Secondary | Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC) | PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication. | Posted | Median | Full Range | mcg/L*hr | Week 2 of course 1 |
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| Secondary | Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification | Epidermal growth factor receptor (EFGR) is a protein found on the surface of cells to which epidermal growth factor (EGF) binds. When EGF attaches to EGFR, it activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. | Epidermal growth factor receptor is only possible with tumor sample, which is only potentially available from supratentorial malignant glioma patients treated on Stratum-1B and Stratum-2. Of 10 Stratum-1B and 3 Stratum-2 patients (n=13), tumor material was available from 11 patients (8 in Stratum-1A and 3 in Stratum-2). | Posted | Number | Participants | Pre-treatment |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stratum IA at Dose 100 mg/m^2 | Brain Stem Glioma patients treated at 100 mg/m2 | 2 | 6 | 6 | 6 | ||
| EG001 | Stratum IA at Dose 250 mg/m^2 | Brain Stem Glioma patients treated at 250 mg/m2 | 15 | 43 | 43 | 43 | ||
| EG002 | Stratum IA at Dose 375 mg/m^2 | Brain Stem Glioma patients treated at 375 mg/m2 | 5 | 7 | 7 | 7 | ||
| EG003 | Stratum IB at Dose 100 mg/m^2 | Patients with STMG treated at 100 mg/m2 | 1 | 2 | 2 | 2 | ||
| EG004 | Stratum IB at Dose 250 mg/m^2 | Patients with STMG treated at 250 mg/m2 | 1 | 3 | 3 | 3 | ||
| EG005 | Stratum IB at Dose 375 mg/m^2 | Patients with STMG treated at 375 mg/m2 | 5 | 5 | 5 | 5 | ||
| EG006 | Stratum II at Dose 100 mg/m^2 | Patients with STMG treated at 100 mg/m2 who are receiving EIACD | 1 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Gastrointestinal disorders | Systematic Assessment |
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| Bilirubin | Investigations | Systematic Assessment |
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| CNS hemorrhage/bleeding | Nervous system disorders | Systematic Assessment |
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| Confusion | Psychiatric disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Death not associated with CTCAE term (Disease progression NOS ) | General disorders | Systematic Assessment |
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| Dehydration | Gastrointestinal disorders | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | Systematic Assessment |
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| Diarrhea patients without colostomy | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue (lethargy, malaise, asthenia) | General disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Hemoglobin (Hgb) | Blood and lymphatic system disorders | Systematic Assessment |
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| Hydrocephalus | Nervous system disorders | Systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Infection with normal ANC or Grade 1 or 2 neutrophils (Bladder (urinary) ) | Infections and infestations | Systematic Assessment |
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| Infection with normal ANC or Grade 1 or 2 neutrophils (Conjunctiva ) | Infections and infestations | Systematic Assessment |
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| Infection with normal ANC or Grade 1 or 2 neutrophils (Skin (cellulitis) ) | Infections and infestations | Systematic Assessment |
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| Infection with unknown ANC (Brain (encephalitis, infectious) ) | Infections and infestations | Systematic Assessment |
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| Infection without neutropenia | Infections and infestations | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Nail changes | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Neurology - Other | Nervous system disorders | Systematic Assessment |
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| Neuropathy - cranial | Nervous system disorders | Systematic Assessment |
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| Neuropathy - sensory | Nervous system disorders | Systematic Assessment |
| ||
| Neuropathy: cranial (CN IX Motor-pharynx; Sensory-ear, pharynx, tongue ) | Nervous system disorders | Systematic Assessment |
| ||
| Neutrophils/granulocytes (ANC/AGC) | Investigations | Systematic Assessment |
| ||
| Nystagmus | Nervous system disorders | Systematic Assessment |
| ||
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
| ||
| Somnolence/depressed level of consciousness | Nervous system disorders | Systematic Assessment |
| ||
| Speech impairment (e.g., dysphasis or aphasia) | Nervous system disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Weight loss | General disorders | Systematic Assessment |
| ||
| Uric acid, serum-high (hyperuricemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Neuropathy: motor | Nervous system disorders | Systematic Assessment |
| ||
| Fibrinogen | Investigations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Investigations | Systematic Assessment |
| ||
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Investigations | Systematic Assessment |
| ||
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Alkaline phosphatase | Investigations | Systematic Assessment |
| ||
| Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Amylase | Investigations | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Ataxia (incoordination) | Nervous system disorders | Systematic Assessment |
| ||
| Auditory/Ear - Other (Specify, __) | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Bicarbonate, serum-low | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Calcium, serum-high (hypercalcemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Cheilitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Cognitive disturbance | Nervous system disorders | Systematic Assessment |
| ||
| Confusion | Psychiatric disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constitutional Symptoms - Other (Specify, __) | General disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Creatinine | Investigations | Systematic Assessment |
| ||
| Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae) | Endocrine disorders | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dermatology/Skin - Other (Specify, __) | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Dry eye syndrome | Eye disorders | Systematic Assessment |
| ||
| Dry mouth/salivary gland (xerostomia) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fatigue (asthenia, lethargy, malaise) | General disorders | Systematic Assessment |
| ||
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders | Systematic Assessment |
| ||
| Fibrinogen | Investigations | Systematic Assessment |
| ||
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Flushing | Vascular disorders | Systematic Assessment |
| ||
| GGT (gamma-Glutamyl transpeptidase) | Investigations | Systematic Assessment |
| ||
| Gastritis (including bile reflux gastritis) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastrointestinal - Other (Specify, __) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Glucose, serum-low (hypoglycemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hair loss/alopecia (scalp or body) | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Heartburn/dyspepsia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hemoglobin | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Hot flashes/flushes | Vascular disorders | Systematic Assessment |
| ||
| Incontinence, urinary | Renal and urinary disorders | Systematic Assessment |
| ||
| Infection - Other (Specify, __) | Infections and infestations | Systematic Assessment |
| ||
| Insomnia | Psychiatric disorders | Systematic Assessment |
| ||
| Keratitis (corneal inflammation/corneal ulceration) | Eye disorders | Systematic Assessment |
| ||
| Leukocytes (total WBC) | Investigations | Systematic Assessment |
| ||
| Lymphopenia | Investigations | Systematic Assessment |
| ||
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Memory impairment | Nervous system disorders | Systematic Assessment |
| ||
| Metabolic/Laboratory - Other (Specify, __) | Investigations | Systematic Assessment |
| ||
| Nail changes | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Neurology - Other (Specify, __) | Nervous system disorders | Systematic Assessment |
| ||
| Neuropathy: motor | Nervous system disorders | Systematic Assessment |
| ||
| Neuropathy: sensory | Nervous system disorders | Systematic Assessment |
| ||
| Neutrophils/granulocytes (ANC/AGC) | Investigations | Systematic Assessment |
| ||
| Nystagmus | Nervous system disorders | Systematic Assessment |
| ||
| Ocular surface disease | Eye disorders | Systematic Assessment |
| ||
| Ocular/Visual - Other (Specify, __) | Eye disorders | Systematic Assessment |
| ||
| Ophthalmoplegia/diplopia (double vision) | Eye disorders | Systematic Assessment |
| ||
| Palpitations | Cardiac disorders | Systematic Assessment |
| ||
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Platelets | Investigations | Systematic Assessment |
| ||
| Potassium, serum-high (hyperkalemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Pulmonary/Upper Respiratory - Other (Specify, __) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Rash/desquamation | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Renal/Genitourinary - Other (Specify, __) | Renal and urinary disorders | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
| ||
| Sodium, serum-high (hypernatremia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Somnolence/depressed level of consciousness | Nervous system disorders | Systematic Assessment |
| ||
| Speech impairment (e.g., dysphasia or aphasia) | Nervous system disorders | Systematic Assessment |
| ||
| Taste alteration (dysgeusia) | Nervous system disorders | Systematic Assessment |
| ||
| Triglyceride, serum-high (hypertriglyceridemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Uric acid, serum-high (hyperuricemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Urinary frequency/urgency | Renal and urinary disorders | Systematic Assessment |
| ||
| Urinary retention (including neurogenic bladder) | Renal and urinary disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Weight gain | Investigations | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mehmet Kocak | Operations and Biostatistics Center for Pediatric Brain Tumor Consortium (PBTC) | 9015952947 | mehmet.kocak@stjude.org |
| ID | Term |
|---|---|
| D000077156 | Gefitinib |
| D011878 | Radiotherapy |
| D011827 | Radiation |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|
|
|
|
|
|
|
|
|
|
| OG003 | Dose 375 mg/m^2 of Gefitinib | This cohort includes all Phase-I patients treated at 375 mg/m^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation. |
|
|
| OG003 | Dose 375 mg/m^2 of Gefitinib | This cohort includes all Phase-I patients treated at 375 mg/m^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation. |
|
|
| OG003 | Dose 375 mg/m^2 of Gefitinib | This cohort includes all Phase-I patients treated at 375 mg/m^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation. |
|
|
| OG003 | Dose 375 mg/m^2 of Gefitinib | This cohort includes all Phase-I patients treated at 375 mg/m^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation. |
|
|
| OG003 | Dose 375 mg/m^2 of Gefitinib | This cohort includes all Phase-I patients treated at 375 mg/m^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation. |
|
|
|