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
3 Years
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy
Outcome 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 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.
Outcome Time Frame:
Day 1 of gefitinib therapy to end of week 8
Safety Issue:
Yes
Principal Investigator
Jeffrey R. Geyer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Seattle Children's Hospital
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000069490
NCT ID:
NCT00042991
Start Date:
August 2002
Completion Date:
March 2010
Related Keywords:
- Brain and Central Nervous System Tumors
- untreated childhood brain stem glioma supratentorial malignant glioma
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Brain Stem Neoplasms
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| UCSF Comprehensive Cancer Center | San Francisco, California 94115 |
| Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital | Houston, Texas 77030-2399 |
