Radiation Therapy and Stereotactic Radiosurgery With or Without Temozolomide or Erlotinib in Treating Patients With Brain Metastases Secondary to Non-Small Cell Lung Cancer
2018년 2월 9일 업데이트: National Cancer Institute (NCI)
A Phase III Trial Comparing Whole Brain Radiation and Stereotactic Radiosurgery Alone Versus With Temozolomide or Erlotinib in Patients With Non-Small Cell Lung Cancer and 1-3 Brain Metastases
This randomized phase III trial is studying whole-brain radiation therapy and stereotactic radiosurgery with or without temozolomide or erlotinib to see how well they work compared to whole-brain radiation therapy and stereotactic radiosurgery in treating patients with brain metastases secondary to non-small cell lung cancer.
Radiation therapy uses high-energy x-rays to kill tumor cells.
Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue.
Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die.
Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by blocking blood flow to the tumor.
It is not yet known whether radiation therapy and stereotactic radiosurgery are more effective with or without temozolomide or erlotinib in treating brain metastases.
연구 개요
상태
종료됨
상세 설명
PRIMARY OBJECTIVES:
I. Compare survival in patients with non-small cell lung cancer and brain metastases treated with whole brain radiotherapy and stereotactic radiosurgery with vs without temozolomide or erlotinib.
SECONDARY OBJECTIVES:
I. Compare time to CNS progression in patients treated with these regimens. II. Compare quality-adjusted survival in patients treated with these regimens. III. Compare 3-month quality of life in patients treated with these regimens. IV. Compare the 6-month performance status of patients treated with these regimens.
V. Compare 6-month steroid dependence in patients treated with these regimens. VI. Compare cause of death (neurologic vs other) in patients treated with these regimens.
VII. Determine the effects of non-protocol chemotherapy in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age and the presence of extracranial metastases (< 65 years old AND no extracranial metastases vs ≥ 65 years old OR extracranial metastases), number of metastases (1 vs 2 or 3), and extent of extracranial disease (none vs present). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.
ARM II: Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ARM III: Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
In all arms, patients with recurrent brain metastases may undergo additional stereotactic radiosurgery.
Quality of life is assessed at baseline and at 3, 6, 9, 12, 18, and 24 months.
Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
연구 유형
중재적
등록 (실제)
126
단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Arizona
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Scottsdale, Arizona, 미국, 85260
- Arizona Oncology Services Foundation
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Scottsdale, Arizona, 미국, 85260
- Scottsdale Health Care-Osborn
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California
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Burbank, California, 미국, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Los Angeles, California, 미국, 90027
- Kaiser Permanente Los Angeles Medical Center
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Pomona, California, 미국, 91767
- Pomona Valley Hospital Medical Center
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Colorado
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Grand Junction, Colorado, 미국, 81501
- Saint Mary's Hospital and Regional Medical Center
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Delaware
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Newark, Delaware, 미국, 19718
- Christiana Care Health System-Christiana Hospital
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Florida
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Jacksonville, Florida, 미국, 32207
- Baptist MD Anderson Cancer Center
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Jacksonville, Florida, 미국, 32258
- Baptist Medical Center South
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Jacksonville, Florida, 미국, 32207
- Integrated Community Oncology Network-Southside Cancer Center
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Jacksonville Beach, Florida, 미국, 32250
- Integrated Community Oncology Network-Florida Cancer Center Beaches
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Miami, Florida, 미국, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Orange Park, Florida, 미국, 32073
- 21st Century Oncology-Orange Park
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Orlando, Florida, 미국, 32806
- UF Cancer Center at Orlando Health
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Palatka, Florida, 미국, 32177
- 21st Century Oncology-Palatka
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Panama City, Florida, 미국, 32401
- Bay Medical Center
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Saint Augustine, Florida, 미국, 32086
- Integrated Community Oncology Network-Flager Cancer Center
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Tallahassee, Florida, 미국, 32308
- Tallahassee Memorial Healthcare
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Georgia
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Columbus, Georgia, 미국, 31904
- John B Amos Cancer Center
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Idaho
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Boise, Idaho, 미국, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Illinois
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Arlington Heights, Illinois, 미국, 60005
- Northwest Community Hospital
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Chicago, Illinois, 미국, 60611
- Northwestern University
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Harvey, Illinois, 미국, 60426
- Ingalls Memorial Hospital
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Springfield, Illinois, 미국, 62702
- Saint John's Hospital
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Indiana
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Fort Wayne, Indiana, 미국, 46805
- Parkview Hospital Randallia
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Hammond, Indiana, 미국, 46320
- Franciscan Saint Margaret Health-Hammond Campus
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Indianapolis, Indiana, 미국, 46202
- IU Health Methodist Hospital
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Iowa
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Dubuque, Iowa, 미국, 52001
- Finley Hospital
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Kentucky
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Louisville, Kentucky, 미국, 40207
- Norton Suburban Hospital and Medical Campus
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Maryland
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Baltimore, Maryland, 미국, 21201
- University of Maryland/Greenebaum Cancer Center
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Baltimore, Maryland, 미국, 21229
- Saint Agnes Hospital
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Massachusetts
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Ann Arbor, Michigan, 미국, 48109
- University of Michigan Comprehensive Cancer Center
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Detroit, Michigan, 미국, 48201
- Wayne State University/Karmanos Cancer Institute
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Kalamazoo, Michigan, 미국, 49007
- West Michigan Cancer Center
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Minnesota
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Burnsville, Minnesota, 미국, 55337
- Fairview Ridges Hospital
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Coon Rapids, Minnesota, 미국, 55433
- Mercy Hospital
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Edina, Minnesota, 미국, 55435
- Fairview-Southdale Hospital
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Fridley, Minnesota, 미국, 55432
- Unity Hospital
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Minneapolis, Minnesota, 미국, 55407
- Abbott-Northwestern Hospital
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Minneapolis, Minnesota, 미국, 55455
- University of Minnesota/Masonic Cancer Center
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Robbinsdale, Minnesota, 미국, 55422
- North Memorial Medical Health Center
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Saint Cloud, Minnesota, 미국, 56303
- Coborn Cancer Center at Saint Cloud Hospital
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Saint Cloud, Minnesota, 미국, 56303
- Saint Cloud Hospital
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Saint Louis Park, Minnesota, 미국, 55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Louis Park, Minnesota, 미국, 55416
- Metro Minnesota Community Oncology Research Consortium
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Saint Paul, Minnesota, 미국, 55102
- United Hospital
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Waconia, Minnesota, 미국, 55387
- Ridgeview Medical Center
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Missouri
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Saint Louis, Missouri, 미국, 63110
- Saint Louis University Hospital
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Nevada
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Las Vegas, Nevada, 미국, 89106
- Nevada Cancer Research Foundation CCOP
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Reno, Nevada, 미국, 89502
- Renown Regional Medical Center
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New Jersey
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New Brunswick, New Jersey, 미국, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
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Red Bank, New Jersey, 미국, 07701
- Riverview Medical Center/Booker Cancer Center
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Sparta, New Jersey, 미국, 07871
- Sparta Cancer Treatment Center
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New York
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Rochester, New York, 미국, 14642
- University of Rochester
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North Carolina
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Asheville, North Carolina, 미국, 28801
- Mission Hospital-Memorial Campus
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Ohio
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Akron, Ohio, 미국, 44304
- Summa Akron City Hospital/Cooper Cancer Center
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Cleveland, Ohio, 미국, 44195
- Cleveland Clinic Foundation
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Oklahoma
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Tulsa, Oklahoma, 미국, 74136
- Natalie Warren Bryant Cancer Center at Saint Francis
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Pennsylvania
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Drexel Hill, Pennsylvania, 미국, 19026
- Delaware County Memorial Hospital
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Philadelphia, Pennsylvania, 미국, 19111
- Fox Chase Cancer Center
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Philadelphia, Pennsylvania, 미국, 19107
- Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, 미국, 19103
- Radiation Therapy Oncology Group
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West Reading, Pennsylvania, 미국, 19611
- Reading Hospital
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South Carolina
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Charleston, South Carolina, 미국, 29425
- Medical University of South Carolina
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Tennessee
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Knoxville, Tennessee, 미국, 37916
- Thompson Cancer Survival Center
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Texas
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Arlington, Texas, 미국, 76012
- Arlington Cancer Center
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Dallas, Texas, 미국, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Galveston, Texas, 미국, 77555-0565
- University of Texas Medical Branch
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Houston, Texas, 미국, 77030
- M D Anderson Cancer Center
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Utah
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Murray, Utah, 미국, 84107
- Intermountain Medical Center
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Ogden, Utah, 미국, 84403
- McKay-Dee Hospital Center
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Salt Lake City, Utah, 미국, 84112
- Huntsman Cancer Institute/University of Utah
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Salt Lake City, Utah, 미국, 84143
- LDS Hospital
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Virginia
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Norfolk, Virginia, 미국, 23507
- Sentara Norfolk General Hospital
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Richmond, Virginia, 미국, 23298
- Virginia Commonwealth University/Massey Cancer Center
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Washington
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Seattle, Washington, 미국, 98101
- Virginia Mason Medical Center
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Wisconsin
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Madison, Wisconsin, 미국, 53792
- University of Wisconsin Hospital and Clinics
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Milwaukee, Wisconsin, 미국, 53226
- Froedtert and the Medical College of Wisconsin
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Racine, Wisconsin, 미국, 53405
- Wheaton Franciscan Cancer Care - All Saints
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Manitoba
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Winnipeg, Manitoba, 캐나다, R3E 0V9
- CancerCare Manitoba
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Ontario
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Ottawa, Ontario, 캐나다, K1Y 4E9
- Ottawa Hospital-Civic Campus
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Quebec
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Montreal, Quebec, 캐나다, H2W 1S6
- McGill University Department of Oncology
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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
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Histologically confirmed non-small cell lung cancer
One to 3 intraparenchymal brain metastases by contrast-enhanced MRI, meeting the following criteria:
- Well circumscribed tumor(s)
Maximum diameter ≤ 4.0 cm
- If multiple lesions are present and one lesion is at the maximum diameter, the other lesions must not exceed 3.0 cm in maximum diameter
- No metastases within 10 mm of the optic apparatus such that a portion of the optic nerve or chiasm would be included in the high-dose stereotactic radiosurgery boost field
- No metastases in the brainstem, midbrain, pons, or medulla
No prior complete resection of all known brain metastases
- Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter
No clinical or radiographic evidence of progression (other than study lesion[s]) within the past month
- Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease
Stable extracranial metastases allowed
- No known or pre-existing liver metastases
- No leptomeningeal metastases by MRI or cerebrospinal fluid evaluation
- Synchronous brain metastases at initial diagnosis allowed
- Performance status - Zubrod 0-1
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
- AST < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 2 times ULN unless due to elevated bone metastases
- Total bilirubin normal
- Lactic dehydrogenase < 2 times ULN
- Creatinine < 1.5 times ULN
No clinically active interstitial lung disease
- Chronic stable asymptomatic radiographic changes allowed
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Neurologic function status 0-2
- No other major medical illness or psychiatric impairment that would preclude study participation
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to erlotinib or temozolomide
- No concurrent immunotherapy
- No concurrent biologic therapy, excluding growth factors and epoetin alfa
- No prior temozolomide or erlotinib
No other concurrent chemotherapy during study radiotherapy
Other concurrent chemotherapy allowed after study radiotherapy, except for the following:
- Temozolomide or erlotinib (arm I only)
- Erlotinib (arm II only)
- Temozolomide (arm III only)
- No prior cranial radiotherapy
- No concurrent intensity-modulated radiotherapy
Concurrent radiotherapy to painful bone lesions allowed
- No concurrent radiotherapy to more than 15% of bone marrow
- No other concurrent therapy for brain metastases unless a recurrence is detected
- More than 30 days since prior investigational drugs
No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following (for patients randomized to receive erlotinib):
- Phenytoin
- Carbamazepine
- Rifampin
- Phenobarbital
- Primidone
- Oxcarbazepine
- No other concurrent investigational drugs
- No concurrent Hypericum perforatum (St. John's wort)
- No drugs that alter gastric pH (e.g., proton pump inhibitors or H2 antagonists) within 4 hours after erlotinib administration (arm III patients only)
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: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Arm I
Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19.
Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.
|
Patients undergo radiation therapy once daily for approximately 3 weeks
다른 이름들:
Patients undergo surgery after radiation therapy
다른 이름들:
|
|
실험적: Arm II
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21.
Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5.
Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
|
구두로 주어진
다른 이름들:
Patients undergo radiation therapy once daily for approximately 3 weeks
다른 이름들:
Patients undergo surgery after radiation therapy
다른 이름들:
|
|
실험적: Arm III
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
|
구두로 주어진
다른 이름들:
Patients undergo radiation therapy once daily for approximately 3 weeks
다른 이름들:
Patients undergo surgery after radiation therapy
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall Survival
기간: From randomization to date of death or last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
Survival time is defined as time from randomization to date of death from any cause and estimated by the Kaplan-Meier method.
Patients last known to be alive are censored at date of last contact.
|
From randomization to date of death or last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Rate of CNS Progression (One Year)
기간: From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
CNS progression is defined as any increase in perpendicular bi-dimensional tumor area for any of the 1-3 tracked brain metastases, by any amount, or the appearance of any new brain metastasis on a follow-up MRI (SRS planning scan will not be used to evaluate CNS progression).
For lesions smaller than 1 cm in maximum diameter, a maximum increase of 50% in perpendicular bi-dimensional treatment area is necessary to score as progression.
This caveat is included to account for potential variability in measurement, which is most susceptible to proportionate errors at smaller sizes.
For greater than 1 cm lesions, the definition uses a 25% rule for change.
Rates of CNS progression estimated by the cumulative incidence method, with death treated as a competing risk.
|
From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
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Quality-adjusted Survival as Measured by EuroQol 5-dimension Instrument
기간: From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
Quality-adjusted life years (QALY) incorporate the societal-based utilities of health states into expected life years for a health condition.
The QALY model is QALY(h,y) where h is a health state and y is the years of life.
Higher quality-adjusted life year values represent a better outcome.
A patient's health state will be determined from the index score of the EQ-5D-5L patient questionnaire.The EQ-5D-5L is a 2-part self-assessment questionnaire, a 5-item index score and a visual analogue scale, but only the index score is used for quality-adjusted survival.
The index score has 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme).
The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state).
|
From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
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Change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) Score at 3 Months
기간: From randomization to three months.
|
The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a 19-item self-report instrument designed to measure multidimensional quality of life in patients with brain cancer.
It is to be administered with the FACT-General.
There are 5 responses options, with 0=Not a lot and 4=Very much.
All items are added together to obtain a total score, which ranges from 0 to 76. Certain items must be reversed before it is added by subtracting the response from 4. It requires at least 50% of the items to be completed while the overall response rate of the FACT-Br including the FACT-G must be greater than 80%.
If items are missing, the subscale scores can be prorated.
A higher score indicates better QOL.
A change of 5 points will be considered a minimal clinically meaningful change.
Change from baseline at three months (3 month score - baseline score) will be categorized as improvement if increased, stable if no change, or deterioration if decreased.
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From randomization to three months.
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Change in Performance Status at Six Months
기간: From randomization to six months.
|
Compared between two treatment arms using a two-group chi-squared test.
Zubrod score will be collected at baseline and follow-up.
The Zubrod performance score runs from 0 to 5, with 0 denoting perfect health and 5 death.
Change from baseline is calculated as 6-month value - baseline value.
Patients with a baseline score who have died by six months will be included in the analysis with a score of 5 at six months.
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From randomization to six months.
|
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Change in Steroid Dependence at Six Months
기간: From randomization to six months.
|
Daily steroid dose will be collected at baseline and follow-up, as one of the following: 0-4 mg, >4 to ≤ 8 mg, >8 to ≤12 mg, and >12 mg.
Change from baseline at six months will be evaluated to have decreased, remained stable, or increased, based on these categories.
|
From randomization to six months.
|
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Cause of Death (Neurologic vs Other)
기간: From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
Patients were considered to have died neurologic deaths (coded as "Brain Metastases") if they had stable systemic disease and progressive neurologic disease consisting of expanding intracranial masses, CNS hemorrhages, hydrocephalus resulting in herniation or fulminant meningeal carcinomatosis.
|
From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Paul Sperduto, Radiation Therapy Oncology Group
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 (실제)
2004년 10월 6일
기본 완료 (실제)
2011년 6월 14일
연구 완료 (실제)
2012년 4월 1일
연구 등록 날짜
최초 제출
2004년 11월 9일
QC 기준을 충족하는 최초 제출
2004년 11월 8일
처음 게시됨 (추정)
2004년 11월 9일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 3월 9일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 2월 9일
마지막으로 확인됨
2018년 2월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2009-00720 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- U10CA021661 (미국 NIH 보조금/계약)
- CDR0000389490
- RTOG 0320 (기타 식별자: Radiation Therapy Oncology Group)
- RTOG-0320 (기타 식별자: CTEP)
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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Ipsen완전한
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Emory University모병신경 모세포종 | 난치성 신경모세포종 | 재발성 신경모세포종미국
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