Radiation Therapy and Stereotactic Radiosurgery With or Without Temozolomide or Erlotinib in Treating Patients With Brain Metastases Secondary to Non-Small Cell Lung Cancer
2018年2月9日 更新者：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.
調査の概要
状態
終了しました
詳細な説明
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.
研究の種類
介入
入学 (実際)
126
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arizona
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Scottsdale、Arizona、アメリカ、85260
- Arizona Oncology Services Foundation
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Scottsdale、Arizona、アメリカ、85260
- Scottsdale Health Care-Osborn
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California
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Burbank、California、アメリカ、91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Los Angeles、California、アメリカ、90027
- Kaiser Permanente Los Angeles Medical Center
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Pomona、California、アメリカ、91767
- Pomona Valley Hospital Medical Center
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Colorado
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Grand Junction、Colorado、アメリカ、81501
- Saint Mary's Hospital and Regional Medical Center
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Delaware
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Newark、Delaware、アメリカ、19718
- Christiana Care Health System-Christiana Hospital
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Florida
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Jacksonville、Florida、アメリカ、32207
- Baptist MD Anderson Cancer Center
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Jacksonville、Florida、アメリカ、32258
- Baptist Medical Center South
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Jacksonville、Florida、アメリカ、32207
- Integrated Community Oncology Network-Southside Cancer Center
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Jacksonville Beach、Florida、アメリカ、32250
- Integrated Community Oncology Network-Florida Cancer Center Beaches
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Miami、Florida、アメリカ、33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Orange Park、Florida、アメリカ、32073
- 21st Century Oncology-Orange Park
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Orlando、Florida、アメリカ、32806
- UF Cancer Center at Orlando Health
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Palatka、Florida、アメリカ、32177
- 21st Century Oncology-Palatka
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Panama City、Florida、アメリカ、32401
- Bay Medical Center
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Saint Augustine、Florida、アメリカ、32086
- Integrated Community Oncology Network-Flager Cancer Center
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Tallahassee、Florida、アメリカ、32308
- Tallahassee Memorial HealthCare
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Georgia
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Columbus、Georgia、アメリカ、31904
- John B Amos Cancer Center
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Idaho
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Boise、Idaho、アメリカ、83706
- Saint Alphonsus Cancer Care Center-Boise
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Illinois
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Arlington Heights、Illinois、アメリカ、60005
- Northwest Community Hospital
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Chicago、Illinois、アメリカ、60611
- Northwestern University
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Harvey、Illinois、アメリカ、60426
- Ingalls Memorial Hospital
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Springfield、Illinois、アメリカ、62702
- Saint John's Hospital
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Indiana
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Fort Wayne、Indiana、アメリカ、46805
- Parkview Hospital Randallia
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Hammond、Indiana、アメリカ、46320
- Franciscan Saint Margaret Health-Hammond Campus
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Indianapolis、Indiana、アメリカ、46202
- IU Health Methodist Hospital
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Iowa
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Dubuque、Iowa、アメリカ、52001
- Finley Hospital
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Kentucky
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Louisville、Kentucky、アメリカ、40207
- Norton Suburban Hospital and Medical Campus
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Maryland
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Baltimore、Maryland、アメリカ、21201
- University of Maryland/Greenebaum Cancer Center
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Baltimore、Maryland、アメリカ、21229
- Saint Agnes Hospital
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Massachusetts
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Comprehensive Cancer Center
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Detroit、Michigan、アメリカ、48201
- Wayne State University/Karmanos Cancer Institute
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Kalamazoo、Michigan、アメリカ、49007
- West Michigan Cancer Center
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Minnesota
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Burnsville、Minnesota、アメリカ、55337
- Fairview Ridges Hospital
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Coon Rapids、Minnesota、アメリカ、55433
- Mercy Hospital
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Edina、Minnesota、アメリカ、55435
- Fairview-Southdale Hospital
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Fridley、Minnesota、アメリカ、55432
- Unity Hospital
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Minneapolis、Minnesota、アメリカ、55407
- Abbott-Northwestern Hospital
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Minneapolis、Minnesota、アメリカ、55455
- University of Minnesota/Masonic Cancer Center
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Robbinsdale、Minnesota、アメリカ、55422
- North Memorial Medical Health Center
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Saint Cloud、Minnesota、アメリカ、56303
- Coborn Cancer Center at Saint Cloud Hospital
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Saint Cloud、Minnesota、アメリカ、56303
- Saint Cloud Hospital
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Saint Louis Park、Minnesota、アメリカ、55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Louis Park、Minnesota、アメリカ、55416
- Metro Minnesota Community Oncology Research Consortium
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Saint Paul、Minnesota、アメリカ、55102
- United Hospital
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Waconia、Minnesota、アメリカ、55387
- Ridgeview Medical Center
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Missouri
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Saint Louis、Missouri、アメリカ、63110
- Saint Louis University Hospital
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Nevada
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Las Vegas、Nevada、アメリカ、89106
- Nevada Cancer Research Foundation CCOP
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Reno、Nevada、アメリカ、89502
- Renown Regional Medical Center
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New Jersey
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New Brunswick、New Jersey、アメリカ、08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
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Red Bank、New Jersey、アメリカ、07701
- Riverview Medical Center/Booker Cancer Center
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Sparta、New Jersey、アメリカ、07871
- Sparta Cancer Treatment Center
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New York
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Rochester、New York、アメリカ、14642
- University of Rochester
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North Carolina
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Asheville、North Carolina、アメリカ、28801
- Mission Hospital-Memorial Campus
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Ohio
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Akron、Ohio、アメリカ、44304
- Summa Akron City Hospital/Cooper Cancer Center
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Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic Foundation
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Oklahoma
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Tulsa、Oklahoma、アメリカ、74136
- Natalie Warren Bryant Cancer Center at Saint Francis
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Pennsylvania
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Drexel Hill、Pennsylvania、アメリカ、19026
- Delaware County Memorial Hospital
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Philadelphia、Pennsylvania、アメリカ、19111
- Fox Chase Cancer Center
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Philadelphia、Pennsylvania、アメリカ、19107
- Thomas Jefferson University Hospital
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Philadelphia、Pennsylvania、アメリカ、19103
- Radiation Therapy Oncology Group
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West Reading、Pennsylvania、アメリカ、19611
- Reading Hospital
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South Carolina
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Charleston、South Carolina、アメリカ、29425
- Medical University of South Carolina
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Tennessee
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Knoxville、Tennessee、アメリカ、37916
- Thompson Cancer Survival Center
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Texas
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Arlington、Texas、アメリカ、76012
- Arlington Cancer Center
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Dallas、Texas、アメリカ、75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Galveston、Texas、アメリカ、77555-0565
- University of Texas Medical Branch
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Houston、Texas、アメリカ、77030
- M D Anderson Cancer Center
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Utah
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Murray、Utah、アメリカ、84107
- Intermountain Medical Center
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Ogden、Utah、アメリカ、84403
- McKay-Dee Hospital Center
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Salt Lake City、Utah、アメリカ、84112
- Huntsman Cancer Institute/University of Utah
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Salt Lake City、Utah、アメリカ、84143
- LDS Hospital
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Virginia
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Norfolk、Virginia、アメリカ、23507
- Sentara Norfolk General Hospital
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Richmond、Virginia、アメリカ、23298
- Virginia Commonwealth University/Massey Cancer Center
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Washington
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Seattle、Washington、アメリカ、98101
- Virginia Mason Medical Center
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
- University of Wisconsin Hospital and Clinics
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Milwaukee、Wisconsin、アメリカ、53226
- Froedtert and The Medical College of Wisconsin
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Racine、Wisconsin、アメリカ、53405
- Wheaton Franciscan Cancer Care - All Saints
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Manitoba
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Winnipeg、Manitoba、カナダ、R3E 0V9
- CancerCare Manitoba
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Ontario
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Ottawa、Ontario、カナダ、K1Y 4E9
- Ottawa Hospital-Civic Campus
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Quebec
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Montreal、Quebec、カナダ、H2W 1S6
- McGill University Department of Oncology
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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)
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：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
他の名前：
Patients undergo surgery after radiation therapy
他の名前：
|
|
実験的：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.
|
経口投与
他の名前：
Patients undergo radiation therapy once daily for approximately 3 weeks
他の名前：
Patients undergo surgery after radiation therapy
他の名前：
|
|
実験的：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.
|
経口投与
他の名前：
Patients undergo radiation therapy once daily for approximately 3 weeks
他の名前：
Patients undergo surgery after radiation therapy
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Rate of CNS Progression (One Year)
時間枠：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.
|
|
Quality-adjusted Survival as Measured by EuroQol 5-dimension Instrument
時間枠：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.
|
|
Change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) Score at 3 Months
時間枠：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.
|
From randomization to three months.
|
|
Change in Performance Status at Six Months
時間枠：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.
|
From randomization to six months.
|
|
Change in Steroid Dependence at Six Months
時間枠：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.
|
|
Cause of Death (Neurologic vs Other)
時間枠：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.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Paul Sperduto、Radiation Therapy Oncology Group
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2004年10月6日
一次修了 (実際)
2011年6月14日
研究の完了 (実際)
2012年4月1日
試験登録日
最初に提出
2004年11月9日
QC基準を満たした最初の提出物
2004年11月8日
最初の投稿 (見積もり)
2004年11月9日
学習記録の更新
投稿された最後の更新 (実際)
2018年3月9日
QC基準を満たした最後の更新が送信されました
2018年2月9日
最終確認日
2018年2月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2009-00720 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- U10CA021661 (米国 NIH グラント/契約)
- CDR0000389490
- RTOG 0320 (その他の識別子：Radiation Therapy Oncology Group)
- RTOG-0320 (その他の識別子：CTEP)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。