Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas - Full Text View

Purpose

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.

Condition	Intervention	Phase
Untreated Childhood Anaplastic Astrocytoma Untreated Childhood Anaplastic Oligodendroglioma Untreated Childhood Brain Stem Glioma Untreated Childhood Giant Cell Glioblastoma Untreated Childhood Glioblastoma Untreated Childhood Gliomatosis Cerebri Untreated Childhood Gliosarcoma Untreated Childhood Oligodendroglioma	Drug: gefitinib Radiation: radiation therapy Other: pharmacological study Other: laboratory biomarker analysis	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Trial of Gefitinib and Radiation in Pediatric Patients Newly Diagnosed With Brain Stem Tumors or Incompletely Resected Supratentorial Malignant Gliomas With Phase II Limited to Brain Stem Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Gefitinib

Genetic and Rare Diseases Information Center resources: Glioblastoma Oligodendroglioma Glioma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Gliosarcoma Childhood Brain Stem Glioma Gliomatosis Cerebri Neuroepithelioma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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.
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 ] [ Designated as safety issue: No ]
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
Median Survival in Newly Diagnosed Brain Stem Gliomas [ Time Frame: Assessed from the start of therapy until three years after initiation of gefitinib therapy ] [ Designated as safety issue: No ]
Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ] [ Designated as safety issue: No ]
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.
Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ] [ Designated as safety issue: No ]
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.
Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ] [ Designated as safety issue: No ]
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.
Mean Tumor to Gray Matter Ratio Measured at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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.
Mean Tumor to White Matter Ratio Measured at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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.
Peak Serum Concentration of Gefitinib (Cmax) [ Time Frame: Week 2 of course 1 ] [ Designated as safety issue: No ]
Elimination Half Life of Gefitinib (t1/2) [ Time Frame: Week 2 of course 1 ] [ Designated as safety issue: No ]
Clearance of Gefitinib (Cl) [ Time Frame: Week 2 of course 1 ] [ Designated as safety issue: No ]
Time of Maximum Clearance of Gefitinib (Tmax) [ Time Frame: Week 2 of course 1 ] [ Designated as safety issue: No ]
Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC) [ Time Frame: Week 2 of course 1 ] [ Designated as safety issue: No ]
Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification [ Time Frame: Pre-treatment ] [ Designated as safety issue: No ]
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.


Enrollment:	69
Study Start Date:	July 2002
Study Completion Date:	March 2010
Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (gefitinib and radiation therapy) 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.	Drug: gefitinib Given orally Other Name: Iressa Radiation: radiation therapy Undergo standard brain irradiation Other Names: irradiation radiotherapy therapy, radiation Other: pharmacological study Correlative studies Other Name: pharmacological studies Other: laboratory biomarker analysis Correlative studies

Arms

Assigned Interventions

Experimental: Treatment (gefitinib and radiation therapy)

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.

Drug: gefitinib

Given orally

Other Name: Iressa

Radiation: radiation therapy

Undergo standard brain irradiation

Other Names:

irradiation
radiotherapy
therapy, radiation

Other: pharmacological study

Correlative studies

Other Name: pharmacological studies

Other: laboratory biomarker analysis

Correlative studies

Show Detailed Description

Eligibility


Ages Eligible for Study:	3 Years to 21 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Tumor:
- Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT
- Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible
Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration
Prior/concurrent therapy:
- Chemotherapy: no prior therapy allowed, including prior gefitinib treatment
- Radiation therapy (XRT): no prior therapy allowed
- Bone marrow transplant: none prior
- Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs
- Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
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:

Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment
Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs
Patient must not be receiving any other anticancer or experimental drug therapy
Patient must have no uncontrolled infection
Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible
Patients with disseminated disease are not permitted
Patients with spinal disease requiring craniospinal radiation are not eligible
Patients with completely resected supratentorial malignant gliomas patients are ineligible

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00042991

Locations


United States, Tennessee
Pediatric Brain Tumor Consortium
Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Jeffrey Geyer	Pediatric Brain Tumor Consortium

More Information


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00042991 History of Changes
Other Study ID Numbers:	NCI-2012-03022 NCI-2012-03022 PBTC-007 PBTC-007 U01CA081457
Study First Received:	August 5, 2002
Results First Received:	February 9, 2011
Last Updated:	May 15, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Glioblastoma Glioma Astrocytoma Gliosarcoma Oligodendroglioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type	Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Gefitinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016