Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

OBJECTIVES:

• Determine the safety and maximum tolerated dose of gefitinib when combined with brain irradiation in children with newly diagnosed brain stem gliomas (BSG) 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 supratentorial malignant gliomas who are receiving concurrent enzyme-inducing anticonvulsant drugs. (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 Magnetic Resonance Imaging (MRI) parameters to metabolic fludeoxyglucose F 18-positron emission tomography scanning with clinical response or progression in patients treated with this regimen. (Phase II)

• Determine the pharmacokinetics of gefitinib in these patients for both Phase-I and Phase-II.

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.

Eligibility 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 brain stem glioma

Trial Contact Information

Trial Lead Organizations/Sponsors

Pediatric Brain Tumor Consortium

Jeffrey Russell Geyer

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00042991
Information obtained from ClinicalTrials.gov on December 15, 2011

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