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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


Phase 1/Phase 2
3 Years
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

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 PhiladelphiaPhiladelphia, Pennsylvania  19104
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Texas Children's Cancer Center and Hematology Service at Texas Children's HospitalHouston, Texas  77030-2399