AzTrials
AzTrials

Untreated Childhood Anaplastic AstrocytomaPhase 1/2NCT00042991

Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

A Phase 1/2 study testing gefitinib, radiation therapy and pharmacological study in people with Untreated Childhood Anaplastic Astrocytoma and Untreated Childhood Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. This phase I/II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma. Read more about this study

Who is it for?
Ages 3 to 21 years
What is being tested?
gefitinib, radiation therapy and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
1 siteUnited States
Study dates
Jul 2002to Mar 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Tumor:
  • Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT
  • Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible
  • Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration
  • Prior/concurrent therapy:
  • Chemotherapy: no prior therapy allowed, including prior gefitinib treatment
Show all 19Show fewer
  • Radiation therapy (XRT): no prior therapy allowed
  • Bone marrow transplant: none prior
  • Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs
  • Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
  • ANC > 1,000/ul
  • Platelets > 100,000/ul (transfusion independent)
  • Hemoglobin > 8g/dl (may be transfused)
  • Patients may have bone marrow involvement by disease
  • Creatinine < 2 x normal for age or GFR > 70 ml/min/1.73m^2
  • Bilirubin < 1.5 x normal institutional normal for age
  • SGPT (ALT) < 3 x institutional normal for age
  • Pregnant and/or lactating patients are excluded; patients of childbearing potential should not become pregnant and should not father a child during treatment with gefitinib; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • Signed informed consent according to institutional guidelines must be obtained prior to study entry

Who cannot join

  • Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment
  • Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs
  • Patient must not be receiving any other anticancer or experimental drug therapy
  • Patient must have no uncontrolled infection
  • Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible
  • Patients with disseminated disease are not permitted
  • Patients with spinal disease requiring craniospinal radiation are not eligible
  • Patients with completely resected supratentorial malignant gliomas patients are ineligible

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Pediatric Brain Tumor Consortium

    Memphis, Tennessee, 38105

Other trials in United States

About this study

Official title: Phase I/II Trial of Gefitinib 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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To define the safety of gefitinib administered in conjunction with irradiation in children with newly diagnosed non-disseminated diffuse intrinsic brainstem gliomas and newly diagnosed incompletely resected supratentorial malignant gliomas (STMG) not receiving enzyme inducing anticonvulsant drugs (EIACDs).

II. To define the safety of gefitinib in children with newly diagnosed, incompletely resected STMG receiving EIACDs.

III. To assess the safety and efficacy of gefitinib given with radiation therapy in children newly diagnosed with a brainstem glioma as measured by progression-free survival and to estimate the survival distribution.

SECONDARY OBJECTIVES:

  1. To compare hemodynamic magnetic resonance (MR) parameters to metabolic fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) scanning and correlate both with clinical response or progression in this population.

II. To characterize the expression of ErbB1 receptors in tissue from STMG patients using immunohistochemistry and western blot assays.

III. To characterize the pharmacokinetics of gefitinib in the above patient groups and determine the effects of EIACD on the pharmacokinetics.

IV. To explore the pharmacogenetic polymorphisms for gefitinib (e.g., CYP3A4/5 and BCRP) and relate them to gefitinib pharmacokinetics and pharmacodynamics (phenotype-genotype).

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.

Being tested
gefitinib, radiation therapy, pharmacological study, laboratory biomarker analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • gefitinibDrug

    Also called Iressa

    Given orally

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo standard brain irradiation

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00042991
Study groupRoleWhat they receive
Treatment (gefitinib and radiation therapy)ExperimentalPhase I portion: 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. Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose.
Receives: Drug: gefitinib; Radiation: radiation therapy; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy

    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.

    Measured: Day 1 of gefitinib therapy to end of week 8

  2. Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas

    Progression-free survival is defined as the interval from intiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurlogical status) or death for patients who failed or to the last date of follow-up for patients without failure

    Measured: Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks

  3. Median Survival in Newly Diagnosed Brain Stem Gliomas

    Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients

    Measured: Assessed from the start of therapy until three years after initiation of gefitinib therapy

Secondary outcomes (12)

  1. Change in Tumor Volume Measured on Fluid Attenuated Inversion Recovery (FLAIR) Imaging at Before the Protocol Therapy Started and at Two Weeks After Completion of Radiation

    This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. In this particular objective, the study aimed to investigate how radiation+gefitinib affect the tumor volume. Tumor volume is measured using Fluid Attenuated Inversion Recovery (FLAIR) before and after the radiation therapy.

    Measured: Baseline and two weeks post completion of radiation

  2. Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation

    This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Volume enhancing is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain.

    Measured: Baseline and two weeks post completion of radiation

  3. Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation

    This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Diffusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain.

    Measured: Baseline and two weeks post completion of radiation

  4. Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation

    This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Perfusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain.

    Measured: Baseline and two weeks post completion of radiation

  5. Mean Tumor to Gray Matter Ratio Measured at Baseline

    This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal gray matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to gray matter ratio value and the median of these values across patients is reported.

    Measured: Baseline

  6. Mean Tumor to White Matter Ratio Measured at Baseline

    This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal white matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to white matter ratio value and the median of these values across patients is reported.

    Measured: Baseline

  7. Peak Serum Concentration of Gefitinib (Cmax)

    Measured: Week 2 of course 1

  8. Elimination Half Life of Gefitinib (t1/2)

    Measured: Week 2 of course 1

  9. Clearance of Gefitinib (Cl)

    Measured: Week 2 of course 1

  10. Time of Maximum Clearance of Gefitinib (Tmax)

    Measured: Week 2 of course 1

  11. Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC)

    Measured: Week 2 of course 1

  12. Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification

    Epidermal growth factor receptor (EFGR) is a protein found on the surface of cells to which epidermal growth factor (EGF) binds. When EGF attaches to EGFR, it activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply.

    Measured: Pre-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJul 2002
  3. Primary completionFeb 2010
  4. Study completionMar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00042991
Sponsor's protocol ID
NCI-2012-03022
Other IDs
NCI-2012-03022, PBTC-007, PBTC-007, U01CA081457
Status last verified
Dec 2012
First submitted
5 Aug 2002
Last updated
28 May 2014

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing gefitinib, radiation therapy and pharmacological study in people with Untreated Childhood Anaplastic Astrocytoma and Untreated Childhood Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy (time frame: Day 1 of gefitinib therapy to end of week 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00042991.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in