Expired Study
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Seattle, Washington 98105


Purpose:

RATIONALE: 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. PURPOSE: This phase I/II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma.


Study summary:

OBJECTIVES: - Determine the safety and maximum tolerated dose of gefitinib when combined with brain irradiation in children with newly diagnosed brain stem gliomas or incompletely resected supratentorial malignant gliomas (STMG) who are not receiving concurrent enzyme-inducing anticonvulsant drugs (EIACDs). (Phase I closed to accrual effective 10/27/2003). - Determine the safety of this regimen in children with newly diagnosed incompletely resected STMG who are receiving concurrent EIACDs. (Phase I closed to accrual effective 10/27/2003). - Determine the safety and efficacy of this regimen in children with newly diagnosed poor-prognosis brain stem glioma.(Phase II) - Correlate the hemodynamic MRI parameters to metabolic fludeoxyglucose F 18-positron emission tomography scanning with clinical response or progression in patients treated with this regimen. - Determine the pharmacokinetics of gefitinib, including the effects of EIACDs on the pharmacokinetics of this drug, in these patients. 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 is determined, additional patients are treated at the MTD. 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: A total of 170 patients (120 for stratum 1A and 50 for strata 1B and 2 combined) may be accrued for this study within 2 years. (Phase I closed to accrual effective 10/27/2003). A total of 40 patients will be accrued for phase II of this study within 10 months.


Criteria:

DISEASE CHARACTERISTICS: - Diagnosis of 1 of the following: - Newly diagnosed non-disseminated diffuse intrinsic brain stem glioma (BSG) - Newly diagnosed incompletely resected supratentorial malignant glioma, including anaplastic astrocytoma, glioblastoma multiforme, or other high-grade gliomas (Phase I closed to accrual effective 10/27/2003) - Must have residual tumor by postoperative MRI or CT scan - Bone marrow involvement by disease allowed - No disseminated disease - No spinal disease requiring radiotherapy - No evidence of intratumoral hemorrhage PATIENT CHARACTERISTICS: Age - 3 to 21 Performance status - Karnofsky 50-100% OR - Lansky 50-100% Life expectancy - Not specified Hematopoietic - Absolute neutrophil count greater than 1,000/mm^3 * - Platelet count greater than 100,000/mm^3 * - Hemoglobin greater than 8 g/dL (transfusion allowed) NOTE: *Transfusion independent Hepatic - Bilirubin no greater than 1.5 times normal - ALT less than 3 times normal - Albumin at least 2 g/dL - No significant hepatic disease Renal - Creatinine less than 2 times normal OR - Glomerular filtration rate greater than 70 mL/min - No significant renal disease Cardiovascular - No significant cardiac disease - No deep venous or arterial thrombosis within the past 6 weeks Pulmonary - No significant pulmonary disease Other - No uncontrolled infection - No significant gastrointestinal disease - No significant psychiatric disease - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 6 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy - More than 2 weeks since prior colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa) - No prior bone marrow transplantation Chemotherapy - No prior chemotherapy Endocrine therapy - Concurrent corticosteroids allowed if receiving a stable or decreasing dose for at least 1 week before study entry - No concurrent tamoxifen Radiotherapy - See Disease Characteristics - No prior radiotherapy Surgery - See Disease Characteristics - No concurrent neurosurgical procedures for reasons other than progression (e.g., onset of hydrocephalus) Other - No prior gefitinib - No other concurrent anticancer or experimental drug therapy - No concurrent drugs with known corneal toxicity (e.g., chlorpromazine, amiodarone, or chloroquine) - No concurrent enzyme-inducing anticonvulsant drugs for patients with BSG


Study is Available At:


Original ID:

CDR0000069490


NCT ID:

NCT00042991


Secondary ID:

PBTC-007


Study Acronym:


Brief Title:

Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas


Official Title:

A Phase I/II Trial Of ZD1839 (Iressa) 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


Overall Status:

Completed


Study Phase:

Phase 1/Phase 2


Genders:

Both


Minimum Age:

3 Years


Maximum Age:

21 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Pediatric Brain Tumor Consortium


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, I


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

69


Enrollment Type:

Actual


Overall Contact Information

Official Name:Jeffrey R. Geyer, MD
Study Chair
Seattle Children's Hospital

Study Dates

Start Date:August 2002
Completion Date:March 2010
Completion Type:Actual
Primary Completion Date:February 2010
Primary Completion Type:Actual
Verification Date:September 2010
Last Changed Date:September 23, 2010
First Received Date:August 5, 2002

Study Outcomes

Outcome Type:Primary Outcome
Measure: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
Safety Issues:False
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 de
Outcome Type:Primary Outcome
Measure:Median survival in newly diagnosed brain stem gliomas
Time Frame:Assessed from the start of therapy until three years after initiation of gefitinib therapy
Safety Issues:False
Description:Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients
Outcome Type:Primary Outcome
Measure:Number of participants in Phase I Stratum 1A with dose-limiting toxicities observed during the first 8 weeks of gefitinib therapy
Time Frame:Day 1 of gefitinib therapy to end of week 8
Safety Issues:True
Description: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 ob
Outcome Type:Primary Outcome
Measure:Number of participants in Phase I Stratum 1B with dose-limiting toxicities observed during the first 8 weeks of gefitinib therapy
Time Frame:Day 1 of gefitinib therapy to end of week 8
Safety Issues:True
Description:The dose limiting toxicity (DLT) analysis population consists of stratum 1B 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 ob
Outcome Type:Primary Outcome
Measure:Number of participants in Phase I Stratum 2 with dose-limiting toxicities observed during the first 8 weeks of gefitinib therapy
Time Frame:Day 1 of gefitinib therapy to end of week 8
Safety Issues:True
Description:The dose limiting toxicity (DLT) analysis population consists of stratum 2 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 obs
Outcome Type:Secondary Outcome
Measure:Change from Baseline in Volume FLAIR at Two Weeks After Completion of Radiation
Time Frame:Baseline and two weeks post completion of radiation
Safety Issues:False
Description: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 FLAIR is one parameter obtai
Outcome Type:Secondary Outcome
Measure:Change from Baseline in Volume Enhancing at Two Weeks After Completion of Radiation
Time Frame:Baseline and two weeks post completion of radiation
Safety Issues:False
Description: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 o
Outcome Type:Secondary Outcome
Measure:Change from Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation
Time Frame:Baseline and two weeks post completion of radiation
Safety Issues:False
Description: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 ob
Outcome Type:Secondary Outcome
Measure:Change from Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation
Time Frame:Baseline and two weeks post completion of radiation
Safety Issues:False
Description: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 ob
Outcome Type:Secondary Outcome
Measure:Mean Tumor to Gray Matter Ratio Measured at Baseline
Time Frame:Baseline
Safety Issues:False
Description: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
Outcome Type:Secondary Outcome
Measure:Mean Tumor to White Matter Ratio Measured at Baseline
Time Frame:Baseline
Safety Issues:False
Description: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
Outcome Type:Secondary Outcome
Measure:Peak Concentration (cmax)
Time Frame:Week 2 of course 1
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Elimination half life
Time Frame:Week 2 of course 1
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Clearance
Time Frame:Week 2 of course 1
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Time of maximum clearance (tmax)
Time Frame:Week 2 of course 1
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Area under the concentration curve from 0-24 hours (AUC)
Time Frame:Week 2 of course 1
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Number of patients with EGFR amplification
Time Frame:Pre-treatment
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Gefitinib
Description:Gefitinib is supplied as tablets containing 25 mg, 100 mg, or 250 mg of the drug. Study subjects will receive gefitinib once daily. A course is defined as 4-weeks of therapy and in the absence of disease progression, treatment may continue for 13 courses (1 year).
Arm Name:Radiation + Gefitinib
Other Name:ZD1839
Intervention Type:Radiation
Name:Local Irradiation
Description:Study subjects will receive local irradiation using conventional or conformal, volume-based delivery techniques. 180 cGy fractions will be used for all target volumes. Radiation will be given once daily, 5 days/week for six weeks to a total dose of 5580 cGy.
Arm Name:Radiation + Gefitinib

Study Arms

Study Arm Type:Experimental
Arm Name:Radiation + Gefitinib

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Pediatric Brain Tumor Consortium
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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