Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00042991
First received: August 5, 2002
Last updated: May 15, 2014
Last verified: December 2012
  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:


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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
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
Investigators
Principal Investigator: Jeffrey Geyer Pediatric Brain Tumor Consortium
  More Information

No publications provided

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

ClinicalTrials.gov processed this record on October 23, 2014