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Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas

2014년 5월 15일 업데이트: 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.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (실제)

69

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 미국
    • Tennessee
      • Memphis, Tennessee, 미국, 38105
        • Pediatric Brain Tumor Consortium

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

3년 (어린이, 성인)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
다른: 실험실 바이오마커 분석
상관 연구
의약품: 게피티닙
구두로 주어진
다른 이름들:
  • 이레사
다른: 약리학적 연구
상관 연구
다른 이름들:
  • 약리학 연구
방사능: radiation therapy
Undergo standard brain irradiation
다른 이름들:
  • 조사
  • 방사선 요법
  • 치료, 방사선

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy
기간: 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
기간: 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
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
기준선에서 측정된 평균 종양 대 회백질 비율
기간: 기준선
이 연구는 양전자 방출 단층 촬영에서 신경 영상 매개 변수를 특성화하려고 시도합니다. 각 환자에 대해 가장 높은 FDG(FluoroDeoxyGlucose) 흡수에 해당하는 픽셀당 최대 활동을 포함하는 종양을 통한 축상 이미지를 식별하고 종양의 FDG 정의를 기반으로 관심 영역(ROI)을 그렸습니다. 종양 ROI 내의 평균 픽셀 값은 종양/회백질의 비율을 제공하기 위해 정상 회백질에 대한 값으로 정규화되었습니다. 각 환자는 평균 종양 대 회백질 비율 값을 가지며 환자 전체에서 이러한 값의 중앙값이 보고됩니다.
기준선
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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: Week 2 of course 1
Week 2 of course 1
Elimination Half Life of Gefitinib (t1/2)
기간: Week 2 of course 1
Week 2 of course 1
Clearance of Gefitinib (Cl)
기간: Week 2 of course 1
Week 2 of course 1
Time of Maximum Clearance of Gefitinib (Tmax)
기간: Week 2 of course 1
Week 2 of course 1
Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC)
기간: Week 2 of course 1
Week 2 of course 1
Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Cancer Institute (NCI)

수사관

  • 수석 연구원: Jeffrey Geyer, Pediatric Brain Tumor Consortium

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2002년 7월 1일

기본 완료 (실제)

2010년 2월 1일

연구 완료 (실제)

2010년 3월 1일

연구 등록 날짜

최초 제출

2002년 8월 5일

QC 기준을 충족하는 최초 제출

2003년 1월 26일

처음 게시됨 (추정)

2003년 1월 27일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2014년 5월 28일

QC 기준을 충족하는 마지막 업데이트 제출

2014년 5월 15일

마지막으로 확인됨

2012년 12월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

  • NCI-2012-03022 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
  • U01CA081457 (미국 NIH 보조금/계약)
  • PBTC-007 (기타 식별자: CTEP)

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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