Extensive Stage Small Cell Lung CarcinomaPhase 2/3NCT02635009
Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Limited Stage or Extensive Stage Small Cell Lung Cancer
A Phase 2/3 study testing Three-Dimensional Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy in people with Extensive Stage Small Cell Lung Carcinoma and Limited Stage Small Cell Lung Carcinoma, run by NRG Oncology at 281 sites in 2 countries.
Trial summary
This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extensive Stage Small Cell Lung Carcinoma, Limited Stage Small Cell Lung Carcinoma
- What is being tested?
- Three-Dimensional Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 418 participants
- Where
- 281 sitesin 2 countries
- Study dates
- 22 Dec 2015to 4 Sep 2025
- Phase
- Phase 2/3
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration
- High-grade neuroendocrine carcinoma or combined SCLC and NSCLC is permitted.
- Patients must have received chemotherapy and be registered to Step 1 registration no earlier than 7 days and no later than 56 days after completing chemotherapy. Note:
- Post-chemotherapy restaging imaging must be completed no more than 56 days prior to Step 1 registration.
- For patients with extensive-stage small cell lung cancer who are being considered for consolidative thoracic radiotherapy after chemotherapy, concomitant administration of consolidative thoracic radiotherapy and protocol-specified prophylactic cranial irradiation with or without hippocampal avoidance is permitted.
- Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan. To yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan must use the smallest possible axial slice thickness not exceeding 1.5 mm.
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- This MRI must be obtained within 56 days prior to Step 1 registration. Note: The MRI study is mandatory irrespective of randomization to the experimental or control arm of this study.
- Prior to chemotherapy +/- thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following:
- History/physical examination;
- CT of the chest and abdomen with contrast (does not have to be done if the patient has had a positron emission tomography (PET) / CT scan prior to initiating chemotherapy or thoracic radiotherapy);
- MRI of the brain with contrast or diagnostic head CT with contrast;
- For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI or head CT, a PET/CT or bone scan is required to confirm limited-stage SCLC.
- After chemotherapy, patients must be restaged prior to Step 1 registration using the same diagnostic work-up as required pre-chemotherapy. Repeat PET/CT or bone scan is not required. Patients must have:
- History/physical examination within 30 days of Step 1 registration;
- No CNS metastases (Repeat MRI required) within 56 days prior to Step 1 registration;
- No progression in any site;
- Radiographic partial or complete response to chemotherapy in at least one disease site within 56 days prior to Step 1 registration.
- If PET/CT was obtained prior to chemotherapy, either a repeat PET/CT or CT of the chest and abdomen with contrast can be obtained for response assessment.
- Patients who underwent resection for limited-stage SCLC prior to chemotherapy and have no radiographically evident disease for response assessment remain eligible if post-chemotherapy imaging demonstrates no progression.
- Zubrod performance status 0-2 within 30 days prior to Step 1 registration.
- Women of childbearing potential must have a negative qualitative serum pregnancy test =< 14 days prior to Step 1 registration.
- Patients who are primary English or French speakers are eligible
- Patients must sign a study-specific informed consent prior to study entry
- The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (Parts A and B), and COWA. The neurocognitive assessments will be uploaded into the NRG Oncology Rave System for evaluation by Neurocognitive Co-Chair. Once the upload is complete, within 3 business days, a notification email will be sent to the site to proceed to Step 2 registration. At minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible.
- Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall as determined by central assessment by the Neurocognitive Co-Chair.
Who cannot join
- Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
- Radiographic evidence of central nervous system (CNS) metastases
- Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
- Planned concurrent chemotherapy during PCI
- Concurrent atezolizumab permitted
- Concomitant invasive malignancy or invasive malignancy within the past five years other than non-melanomatous skin cancer; history of in situ carcinoma (e.g. ductal carcinoma in situ of breast, in situ carcinoma of the cervix, vulva or larynx) is permitted
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- Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia
- Severe, active comorbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Uncontrolled, clinically significant cardiac arrhythmias
- HIV positive with CD4 count < 200 cells/microliter;
- Note: Patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to Step 1 registration.
- Note: HIV testing is not required for eligibility for this protocol.
- Pregnant or lactating women or women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.
Trial locations and contacts
281 sites in 2 countries.
281 sites in 2 countries
United States270 sites
The Cancer Center of Hawaii-Pali Momi
‘Aiea, Hawaii, 96701
Jefferson Abington Hospital
Abington, Pennsylvania, 19001
Summa Health System - Akron Campus
Akron, Ohio, 44304
Cleveland Clinic Akron General
Akron, Ohio, 44307
Mayo Clinic Health System in Albert Lea
Albert Lea, Minnesota, 56007
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Ascension Saint Vincent Anderson
Anderson, Indiana, 46016
AnMed Health Cancer Center
Anderson, South Carolina, 29621
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Luminis Health Anne Arundel Medical Center
Annapolis, Maryland, 21401
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409
Grady Health System
Atlanta, Georgia, 30303
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Piedmont Hospital
Atlanta, Georgia, 30309
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Northside Hospital
Atlanta, Georgia, 30342
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237
MedStar Good Samaritan Hospital
Baltimore, Maryland, 21239
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706
Northwell Health Imbert Cancer Center
Bay Shore, New York, 11706
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602
Billings Clinic Cancer Center
Billings, Montana, 59101
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Boca Raton Regional Hospital
Boca Raton, Florida, 33486
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Hartford HealthCare - Saint Vincent's Medical Center
Bridgeport, Connecticut, 06606
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Ascension Southeast Wisconsin Hospital - Elmbrook Campus
Brookfield, Wisconsin, 53045
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn, New York, 11215
Crozer-Keystone Regional Cancer Center at Broomall
Broomall, Pennsylvania, 19008
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010
Roswell Park Cancer Institute
Buffalo, New York, 14263
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
University of Vermont Medical Center
Burlington, Vermont, 05401
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Saint Luke's Hospital
Cedar Rapids, Iowa, 52402
Mercy Hospital
Cedar Rapids, Iowa, 52403
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Geauga Hospital
Chardon, Ohio, 44024
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Atrium Health Pineville/LCI-Pineville
Charlotte, North Carolina, 28210
Atrium Health University City/LCI-University
Charlotte, North Carolina, 28262
Chelsea Hospital
Chelsea, Michigan, 48118
Northwestern University
Chicago, Illinois, 60611
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
Adena Regional Medical Center
Chillicothe, Ohio, 45601
McLaren Cancer Institute-Clarkston
Clarkston, Michigan, 48346
Michigan Healthcare Professionals Clarkston
Clarkston, Michigan, 48346
Case Western Reserve University
Cleveland, Ohio, 44106
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland, 21044
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Mount Carmel Health Center West
Columbus, Ohio, 43222
Memorial Sloan Kettering Commack
Commack, New York, 11725
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Northside Hospital-Forsyth
Cumming, Georgia, 30041
Geisinger Medical Center
Danville, Pennsylvania, 17822
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124
Decatur Memorial Hospital
Decatur, Illinois, 62526
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Wentworth-Douglass Hospital
Dover, New Hampshire, 03820
Saint Luke's Hospital of Duluth
Duluth, Minnesota, 55805
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, 18512
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, 54701
Mayo Clinic Health System Eau Claire Hospital-Luther Campus
Eau Claire, Wisconsin, 54703
Crossroads Cancer Center
Effingham, Illinois, 62401
Arnot Ogden Medical Center/Falck Cancer Center
Elmira, New York, 14905
Mercy Cancer Center-Elyria
Elyria, Ohio, 44035
Swedish Medical Center
Englewood, Colorado, 80113
Englewood Hospital and Medical Center
Englewood, New Jersey, 07631
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Michigan Healthcare Professionals Farmington
Farmington Hills, Michigan, 48334
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
McLaren Cancer Institute-Flint
Flint, Michigan, 48532
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
Parkview Hospital Randallia
Fort Wayne, Indiana, 46805
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845
Ascension Saint Francis - Reiman Cancer Center
Franklin, Wisconsin, 53132
University of Texas Medical Branch
Galveston, Texas, 77555-0565
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Adams Cancer Center
Gettysburg, Pennsylvania, 17325
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland, 21061
Crozer Regional Cancer Center at Brinton Lake
Glen Mills, Pennsylvania, 19342
Goshen Center for Cancer Care
Goshen, Indiana, 46526
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311
Marin General Hospital
Greenbrae, California, 94904
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Self Regional Healthcare
Greenwood, South Carolina, 29646
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
The Radiation Oncology Center-Hilton Head/Bluffton
Hilton Head Island, South Carolina, 29926
Edward Hines Jr VA Hospital
Hines, Illinois, 60141
Queen's Medical Center
Honolulu, Hawaii, 96813
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817
UT MD Anderson Cancer Center
Houston, Texas, 77030
Cleveland Clinic Cancer Center Independence
Independence, Ohio, 44131
University of Wisconsin Carbone Cancer Center - Johnson Creek
Johnson Creek, Wisconsin, 53038
Freeman Health System
Joplin, Missouri, 64804
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
North Kansas City Hospital
Kansas City, Missouri, 64116
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin, 53142
Covenant Health Cancer Centers
Knoxville, Tennessee, 37916
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Mayo Clinic Health System-Franciscan Healthcare
La Crosse, Wisconsin, 54601
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Lancaster Radiation Therapy Center
Lancaster, South Carolina, 29720
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
UTMB Cancer Center at Victory Lakes
League City, Texas, 77573
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Condell Memorial Hospital
Libertyville, Illinois, 60048
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Los Angeles General Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Lowell General Hospital
Lowell, Massachusetts, 01854
Michigan Healthcare Professionals Macomb
Macomb, Michigan, 48044
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Mayo Clinic Health Systems-Mankato
Mankato, Minnesota, 56001
Blount Memorial Hospital
Maryville, Tennessee, 37804
Loyola University Medical Center
Maywood, Illinois, 60153
Riddle Memorial Hospital
Media, Pennsylvania, 19063
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060
Mercy Cancer Center
Merced, California, 95340
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Miami Cancer Institute
Miami, Florida, 33176
UH Seidman Cancer Center at Southwest General Hospital
Middleburg Heights, Ohio, 44130
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Aurora Sinai Medical Center
Milwaukee, Wisconsin, 53233
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Community Medical Center
Missoula, Montana, 59804
Atrium Health Union/LCI-Union
Monroe, North Carolina, 28112
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
West Virginia University Healthcare
Morgantown, West Virginia, 26506
McLaren Cancer Institute-Macomb
Mount Clemens, Michigan, 48043
Virtua Memorial
Mount Holly, New Jersey, 08060
McLaren Cancer Institute-Central Michigan
Mount Pleasant, Michigan, 48858
IU Health Ball Memorial Hospital
Muncie, Indiana, 47303
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Yale University
New Haven, Connecticut, 06520
Tulane University School of Medicine
New Orleans, Louisiana, 70112
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Lenox Hill Hospital
New York, New York, 10075
Helen F Graham Cancer Center
Newark, Delaware, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116
Mayo Clinic Radiation Therapy-Northfield
Northfield, Minnesota, 55057
Kaiser Permanente Oakland-Broadway
Oakland, California, 94611
TidalHealth Richard A Henson Cancer Institute
Ocean Pines, Maryland, 21811
Ogden Regional Medical Center
Ogden, Utah, 84405
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Saint Joseph Hospital - Orange
Orange, California, 92868
Orlando Health Cancer Institute
Orlando, Florida, 32806
Vince Lombardi Cancer Clinic - Oshkosh
Oshkosh, Wisconsin, 54904
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
McLaren Cancer Institute-Owosso
Owosso, Michigan, 48867
University Hospitals Parma Medical Center
Parma, Ohio, 44129
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
McLaren Cancer Institute-Northern Michigan
Petoskey, Michigan, 49770
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Jefferson Torresdale Hospital
Philadelphia, Pennsylvania, 19114
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
McLaren-Port Huron
Port Huron, Michigan, 48060
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210
Ascension All Saints Hospital
Racine, Wisconsin, 53405
Kaiser Permanente-Rancho Cordova Cancer Center
Rancho Cordova, California, 95670
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
Penn State Health Saint Joseph Medical Center
Reading, Pennsylvania, 19605
Renown Regional Medical Center
Reno, Nevada, 89502
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Rock Hill Radiation Therapy Center
Rock Hill, South Carolina, 29730
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, 95661
The Permanente Medical Group-Roseville Radiation Oncology
Roseville, California, 95678
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073
Sutter Medical Center Sacramento
Sacramento, California, 95816
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Dartmouth Cancer Center - North
Saint Johnsbury, Vermont, 05819
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan, 49085
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
TidalHealth Peninsula Regional
Salisbury, Maryland, 21801
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051
Memorial Health University Medical Center
Savannah, Georgia, 31404
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, 31405
Atrium Health Cleveland/LCI-Cleveland
Shelby, North Carolina, 28150
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Springfield Memorial Hospital
Springfield, Illinois, 62781
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Staten Island University Hospital
Staten Island, New York, 10305
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Cleveland Clinic Cancer Center Strongsville
Strongsville, Ohio, 44136
Aurora Medical Center in Summit
Summit, Wisconsin, 53066
State University of New York Upstate Medical University
Syracuse, New York, 13210
Moffitt Cancer Center
Tampa, Florida, 33612
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
UM Saint Joseph Medical Center
Towson, Maryland, 21204
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085
Michigan Healthcare Professionals Troy
Troy, Michigan, 48098
Gene Upshaw Memorial Tahoe Forest Cancer Center
Truckee, California, 96161
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
Lewis and Faye Manderson Cancer Center
Tuscaloosa, Alabama, 35401
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301
Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers, Wisconsin, 54241
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Carle Cancer Center
Urbana, Illinois, 61801
Sutter Solano Medical Center/Cancer Center
Vallejo, California, 94589
Virtua Voorhees
Voorhees Township, New Jersey, 08043
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401
Aurora West Allis Medical Center
West Allis, Wisconsin, 53227
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Reading Hospital
West Reading, Pennsylvania, 19611
UHHS-Westlake Medical Center
Westlake, Ohio, 44145
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476
Wheeling Hospital/Schiffler Cancer Center
Wheeling, West Virginia, 26003
Ascension Via Christi Hospitals Wichita
Wichita, Kansas, 67214
Wesley Medical Center
Wichita, Kansas, 67214
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, 54494
Cleveland Clinic Wooster Family Health and Surgery Center
Wooster, Ohio, 44691
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096
WellSpan Health-York Cancer Center
York, Pennsylvania, 17403
Canada11 sites
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
London Regional Cancer Program
London, Ontario, N6A 4L6
CHUM - Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 3E4
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9
Stronach Regional Health Centre at Southlake
Newmarket, Ontario, L3Y 2P9
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, K1H 8L6
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
Québec, Quebec, G1R 2J6
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer
This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component [Non-Inferiority]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component [Efficacy])
SECONDARY OBJECTIVES:
- Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) parts A and B), after PCI versus HA-PCI in SCLC.
II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC.
III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire (QLQ)-Core [C]30 and BN20) between PCI versus HA-PCI for patients with SCLC.
IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC.
- Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC.
VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria.
VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC.
VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy [IMRT]) and PCI (3-dimensional conformal radiation therapy [3DCRT]) using the EuroQual (EQ)-5-Dimensions (5D)-5L.
IX. Correlate miRNA signatures with cognitive failure in SCLC patients who received PCI and HA-PCI.
- Evaluate Apolipoprotein E (APOE) genotyping as potential predictor of neurocognitive decline, hippocampal atrophy after brain irradiation and/or differential benefit from hippocampal avoidance.
XI. Evaluate baseline MR imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI.
TERTIARY OBJECTIVES:
- Collect serum, whole blood, and urine for future translational research analyses.
II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks.
ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks.
After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.
- Being tested
- Three-Dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Three-Dimensional Conformal Radiation TherapyRadiation
Also called 3-dimensional conformal radiation therapy, 3-dimensional radiation therapy, 3D-CRT, Conformal Therapy
daily fractions
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy
daily fractions
| Study group | Role | What they receive |
|---|---|---|
| PCI using 3DCRT | Active comparator | Prophylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT) for 2 weeks, 5 fractions/week. Receives: Radiation: Three-Dimensional Conformal Radiation Therapy |
| PCI with HA using IMRT | Experimental | PCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) for 2 weeks, 5 fractions/week. Receives: Radiation: Intensity-Modulated Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)
The HVLT-R delayed recall test assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials to recall after a 20-minute delay. The score is the sum of the number of words correctly recalled and ranges from 0 to 36, with a higher score indicating better functioning. Deterioration is defined a decrease from baseline of at least 3 points.
Measured: Baseline and six months
Number of Participants With Intracranial Relapse at 12 Months (Phase II)
Intracranial relapse, defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast.
Measured: From baseline to 12 months
Secondary outcomes (35)
Percentage of Participants With Neurocognitive Failure (Phase III)
Neurocognitive failure is defined as the first instance of neurocognitive decline in any of six assessments, as determined my reliable change index: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test (TMT) part A, TMT part B, and Controlled Oral Word Association (COWA). Failure time is defined as time from randomization to failure, death (competing event), or last follow-up (censored). Neurocognitive failure rates are estimated using the cumulative incidence method. The distributions of failure times are compared, which is reported in the statistical analysis results. Six-month rates are reported here. Analysis occurred after all patients had been on study for at least six months.
Measured: Randomization to date of failure, death, or last known follow-up whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
The HVLT-R Total Recall score assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials. Raw score is the sum of the number of targets correctly recalled, ranging from 0 to 36. Higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 5 points.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
he HVLT-R Total Recall score assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials. Raw score is the sum of the number of targets correctly recalled, ranging from 0 to 36. Higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 5 points.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
The HVLT-R Delayed Recall test assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials, this test requires recalling the 12 targets after a 20-minute delay. Raw scores are sum of the number of targets correctly recalled. The score ranges from 0 to 12. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 3 points. Six-month results are reported as the primary endpoint.
Measured: Baseline, 3, 12 months.
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
The HVLT-R Delayed Recall test assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials, this test requires recalling the 12 targets after a 20-minute delay. Raw scores are sum of the number of targets correctly recalled. The score ranges from 0 to 12. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 3 points.
Measured: Baseline, 18, 24 months.
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
The HVLT-R Delayed Recognition assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials and recalling the 12 targets after a 20-minute delay, the test involves then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are the sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified. The score ranges from -12 to 12 for recognition. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 2 points.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
The HVLT-R Delayed Recognition assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials and recalling the 12 targets after a 20-minute delay, the test involves then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are the sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified. The score ranges from -12 to 12 for recognition. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 2 points.
Measured: Baseline, 18, 24 months.
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A, reported here), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order. The score is the amount of time, in seconds, that it takes the patient to complete the maze. The range for Part A is 0 to 180 (3 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 12 seconds.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A, reported here), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order. The score is the amount of time, in seconds, that it takes the patient to complete the maze. The range for Part A is 0 to 180 (3 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 12 seconds.
Measured: Baseline, 18, 24 months.
Number of Participants With Deterioration in TMT Part B Score (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the second part (Part B, reported here), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete the maze. The score range for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 26 seconds.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in TMT Part B Score (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the second part (Part B, reported here), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete the maze. The score range for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 26 seconds.
If reporting a score on a scale, please include the unabbreviated scale title, the minimum and maximum values, and whether higher scores mean a better or worse outcome.
Measured: Baseline, 18, 24 months.
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Deterioration is defined an increase from baseline of at least 12 words.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Deterioration is defined an increase from baseline of at least 12 words.
Measured: Baseline,18, 24 months.
Number of Participants by Highest Grade Adverse Event Reported (Phase III)
Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Measured: From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years.
Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III)
The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III)
The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III)
The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III)
The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Measured: Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
The QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Measured: Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
The QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Measured: Baseline,18, 24 months.
Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months
The Pearson correlation coefficient was calculated for EORTC QLQ-C30 (physical, role, emotional, cognitive, and social functioning domains and global health status) and QLQ-BN20 (motor dysfunction and communication deficit) versus the standardized neurocognitive function (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, COWA, TMT parts A and B) and the Clinical Trial Battery Composite (CTB Comp) score (mean of the z-scores for the six NCF scores) for all patients, treatment arms combined. The Pearson correlation coefficient is computed for each pair of measurements, resulting in 48 correlation coefficients. Possible values range from -1 (negatively correlated) to 1(positively correlated), with 0 indicating no correlation. A correlation with a value in range -0.35 to 0.35 is considered weak and is indicated by "0" in the table. Because of the large number of comparisons, only individual correlation coefficients outside that range are listed here.
Measured: 6 months
Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III)
The incremental cost per quality-adjusted life year (QALY) ratio will be calculated as total cost of the PCI with HA using IMRT arm (Arm 2) minus total cost of the PCI using 3DCRT arm (Arm 1), divided by the quality adjusted survival of the Arm 1 patients minus the quality adjusted survival of Arm 2 patients.
Measured: Baseline to two years
Overall Survival (Phase III)
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 8 months.
Measured: From the date of randomization to the date of death or last follow-up. Maximum follow-up time at time of analysis was 7.2 years.
Intracranial Relapse Rate (Phase III)
Intracranial relapse is defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast. Time to intracranial relapse is defined as time from randomization to the date of first intracranial relapse, last known follow-up (censored), or death without intracranial relapse (competing risk), whichever occurred first. Intracranial relapse rates are estimated using the cumulative incidence method. The distributions of intracranial relapse times are compared between the arms, which is reported in the statistical analysis results. One-year rates are provided here. Analysis occurred at time of the phase III primary analysis.
Measured: From date of randomization to date of intracranial relapse, death, or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.
White Matter Injury and Hippocampal Volume on Neurocognitive Function (Phase III)
Pearson correlation coefficients will be used to assess the effect of hippocampal volume and FLAIR volume change on baseline neurocognitive function, as measured by the HVLT-R, COWA, and TMT, separately for each arm.
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2015 (estimated)
- Study start22 Dec 2015
- Primary completion18 May 2023
- Study completion4 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Extensive Stage Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 418 participants (actual)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Radiation Therapy Oncology Group
- Responsible party
- Sponsor
- Investigators
- Vinai Gondi, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02635009
- Sponsor's protocol ID
- NRG-CC003
- Other IDs
- NCI-2015-01548, NRG-CC003, NRG-CC003, UG1CA189867
- Status last verified
- Jun 2026
- First submitted
- 16 Dec 2015
- Last updated
- 10 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Publications
Gondi V, Pugh SL, Mehta MP, Wefel JS, Tome WA, Sun AY, Grecula J, Redmond KJ, Fogh S, Gaspar L, Konski A, Bovi J, Robinson CG, Corn B, Videtic GM, Lok BH, Yoon HA, Heinzerling JH, DeNittis AS, McGarry RC, Devisetty K, Kundapur V, Wu AJ, McCarron EC, Thibault I, Simon EL, Baschnagel AM, Narayan S, Pollock J, Paulus R, Kachnic LA; NRG Oncology. Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003. J Clin Oncol. 2025 Nov 10;43(32):3516-3525. doi: 10.1200/JCO-25-00221. Epub 2025 Aug 11.
PubMed 40789106Ishibashi A, Kurosaki H, Miura K, Utsumi N, Sakurai H. Influence of Modulation Factor on Treatment Plan Quality and Irradiation Time in Hippocampus-Sparing Whole-Brain Radiotherapy Using Tomotherapy. Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211045497. doi: 10.1177/15330338211045497.
PubMed 34632876