Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 3 to 21 NCI PBTC-007 NCT00042991

Objectives

1. 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).
2. 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).
3. Determine the safety and efficacy of this regimen in children with newly diagnosed poor-prognosis brain stem glioma.
4. 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.
5. Determine the pharmacokinetics of gefitinib, including the effects of EIACDs on the pharmacokinetics of this drug, in these patients.

Entry 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

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

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/mm³ *
• Platelet count greater than 100,000/mm³ *
• 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

Expected Enrollment

A total of 170 patients (120 for stratum 1A and 50 for strata 1B and 2 combined) will 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.

Outcomes

Efficacy
Progression-free survival at 1 year
Safety
Correlation of hemodynamic MRI parameters with clinical response or progression
Maximum tolerated dose of gefitinib
Pharmacokinetics

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 every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Pediatric Brain Tumor Consortium

Jeffrey Geyer, MD, Protocol chair		Ph: 206-987-6664

Registry Information
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
Trial Start Date		2002-08-27
Registered in ClinicalTrials.gov		NCT00042991
Date Submitted to PDQ		2002-06-10
Information Last Verified		2005-12-08
NCI Grant/Contract Number		CA81457

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