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

Sponsors and Collaborators:	Pediatric Brain Tumor Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00042991

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 II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: gefitinib Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Radiation Therapy

Drug Information available for: ZD1839

U.S. FDA Resources

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

Primary Outcome Measures:

Efficacy [ Designated as safety issue: No ]
Progression-free survival at 1 year [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]
Correlation of hemodynamic MRI parameters with clinical response or progression [ Designated as safety issue: No ]
Maximum tolerated dose of gefitinib [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	210
Study Start Date:	August 2002

Detailed Description:

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

PROJECTED ACCRUAL: 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.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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

Locations

United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Pediatric Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Jeffrey R. Geyer, MD

Seattle Children's Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000069490, PBTC-007
Study First Received:	August 5, 2002
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00042991 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated childhood brain stem glioma

Study placed in the following topic categories:

Brain Neoplasms
Brain Stem Glioma, Childhood
Brain Stem Neoplasms
Central Nervous System Diseases
Glioma

Central Nervous System Neoplasms
Brain Diseases
Protein Kinase Inhibitors
Gefitinib
Nervous System Neoplasms

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Brain Stem Neoplasms
Central Nervous System Diseases
Enzyme Inhibitors
Central Nervous System Neoplasms
Brain Diseases
Protein Kinase Inhibitors

Pharmacologic Actions
Brain Neoplasms
Neoplasms
Neoplasms by Site
Therapeutic Uses
Infratentorial Neoplasms
Gefitinib
Nervous System Neoplasms

ClinicalTrials.gov processed this record on July 02, 2009