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Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

15 maja 2014 zaktualizowane przez: National Cancer Institute (NCI)

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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

PRIMARY OBJECTIVES:

I. 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:

I. 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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

69

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Stany Zjednoczone
    • Tennessee
      • Memphis, Tennessee, Stany Zjednoczone, 38105
        • Pediatric Brain Tumor Consortium

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

3 lata do 21 lat (Dziecko, Dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

  • 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
    • 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

Exclusion Criteria:

  • 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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Treatment (gefitinib and radiation therapy)

Phase 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.
Inny: laboratoryjna analiza biomarkerów
Badania korelacyjne
Lek: gefitynib
Podany doustnie
Inne nazwy:
  • Iressa
Inny: badanie farmakologiczne
Badania korelacyjne
Inne nazwy:
  • badania farmakologiczne
Promieniowanie: radiation therapy
Undergo standard brain irradiation
Inne nazwy:
  • naświetlanie
  • radioterapia
  • terapia, promieniowanie

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy
Ramy czasowe: Day 1 of gefitinib therapy to end of week 8
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.
Day 1 of gefitinib therapy to end of week 8
Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas
Ramy czasowe: Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks
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
Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks
Median Survival in Newly Diagnosed Brain Stem Gliomas
Ramy czasowe: Assessed from the start of therapy until three years after initiation of gefitinib therapy
Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients
Assessed from the start of therapy until three years after initiation of gefitinib therapy

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Średni stosunek guza do istoty szarej mierzony na początku badania
Ramy czasowe: Linia bazowa
Niniejsze badanie jest próbą scharakteryzowania parametrów neuroobrazowania z pozytonowej tomografii emisyjnej. Dla każdego pacjenta zidentyfikowano obraz osiowy przez guz zawierający maksymalną aktywność na piksel odpowiadającą najwyższemu wychwytowi fluorodeoksyglukozy (FDG) i narysowano obszar zainteresowania (ROI) w oparciu o definicję guza FDG. Średnie wartości pikseli w ROI guza zostały znormalizowane przez te dla normalnej istoty szarej, aby zapewnić stosunki guza do istoty szarej. Każdy pacjent ma średnią wartość stosunku guza do istoty szarej i podaje się medianę tych wartości u pacjentów.
Linia bazowa
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
Ramy czasowe: Baseline and two weeks post 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.
Baseline and two weeks post completion of radiation
Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation
Ramy czasowe: Baseline and two weeks post 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.
Baseline and two weeks post completion of radiation
Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation
Ramy czasowe: Baseline and two weeks post 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.
Baseline and two weeks post completion of radiation
Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation
Ramy czasowe: Baseline and two weeks post 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.
Baseline and two weeks post completion of radiation
Mean Tumor to White Matter Ratio Measured at Baseline
Ramy czasowe: 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.
Baseline
Peak Serum Concentration of Gefitinib (Cmax)
Ramy czasowe: Week 2 of course 1
Week 2 of course 1
Elimination Half Life of Gefitinib (t1/2)
Ramy czasowe: Week 2 of course 1
Week 2 of course 1
Clearance of Gefitinib (Cl)
Ramy czasowe: Week 2 of course 1
Week 2 of course 1
Time of Maximum Clearance of Gefitinib (Tmax)
Ramy czasowe: Week 2 of course 1
Week 2 of course 1
Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC)
Ramy czasowe: Week 2 of course 1
Week 2 of course 1
Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification
Ramy czasowe: Pre-treatment
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.
Pre-treatment

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

National Cancer Institute (NCI)

Śledczy

  • Główny śledczy: Jeffrey Geyer, Pediatric Brain Tumor Consortium

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 lipca 2002

Zakończenie podstawowe (Rzeczywisty)

1 lutego 2010

Ukończenie studiów (Rzeczywisty)

1 marca 2010

Daty rejestracji na studia

Pierwszy przesłany

5 sierpnia 2002

Pierwszy przesłany, który spełnia kryteria kontroli jakości

26 stycznia 2003

Pierwszy wysłany (Oszacować)

27 stycznia 2003

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

28 maja 2014

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

15 maja 2014

Ostatnia weryfikacja

1 grudnia 2012

Więcej informacji

Terminy związane z tym badaniem

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • NCI-2012-03022 (Identyfikator rejestru: CTRP (Clinical Trial Reporting Program))
  • U01CA081457 (Grant/umowa NIH USA)
  • PBTC-007 (Inny identyfikator: CTEP)

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

produkt wyprodukowany i wyeksportowany z USA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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