Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Limited Stage or Extensive Stage Small Cell Lung Cancer

April 28, 2026 updated by: NRG Oncology

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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.

X. 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:

I. 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.

Study Type

Interventional

Enrollment (Actual)

418

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Newmarket, Ontario, Canada, L3Y 2P9
        • Stronach Regional Health Centre at Southlake
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital and Cancer Center-General Campus
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network-Princess Margaret Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3H 2R9
        • The Research Institute of the McGill University Health Centre (MUHC)
      • Montreal, Quebec, Canada, H2X 3E4
        • CHUM - Centre Hospitalier de l'Universite de Montreal
      • Québec, Quebec, Canada, G1R 2J6
        • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Tuscaloosa, Alabama, United States, 35401
        • Lewis and Faye Manderson Cancer Center
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
    • California
      • Greenbrae, California, United States, 94904
        • Marin General Hospital
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Merced, California, United States, 95340
        • Mercy Cancer Center
      • Oakland, California, United States, 94611
        • Kaiser Permanente Oakland-Broadway
      • Orange, California, United States, 92868
        • Saint Joseph Hospital - Orange
      • Rancho Cordova, California, United States, 95670
        • Kaiser Permanente-Rancho Cordova Cancer Center
      • Roseville, California, United States, 95678
        • The Permanente Medical Group-Roseville Radiation Oncology
      • Roseville, California, United States, 95661
        • Sutter Cancer Centers Radiation Oncology Services-Roseville
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center-Pacific Campus
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Vallejo, California, United States, 94589
        • Sutter Solano Medical Center/Cancer Center
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Swedish Medical Center
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
    • Connecticut
      • Bridgeport, Connecticut, United States, 06606
        • Hartford HealthCare - Saint Vincent's Medical Center
      • New Haven, Connecticut, United States, 06520
        • Yale University
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Boca Raton Regional Hospital
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Fort Lauderdale, Florida, United States, 33316
        • Broward Health Medical Center
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30303
        • Grady Health System
      • Atlanta, Georgia, United States, 30309
        • Piedmont Hospital
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Cumming, Georgia, United States, 30041
        • Northside Hospital-Forsyth
      • Savannah, Georgia, United States, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • ‘Aiea, Hawaii, United States, 96701
        • The Cancer Center of Hawaii-Pali Momi
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Caldwell, Idaho, United States, 83605
        • Saint Alphonsus Cancer Care Center-Caldwell
      • Meridian, Idaho, United States, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83687
        • Saint Alphonsus Cancer Care Center-Nampa
      • Nampa, Idaho, United States, 83687
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • John H Stroger Jr Hospital of Cook County
      • Chicago, Illinois, United States, 60612
        • Rush MD Anderson Cancer Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Hines, Illinois, United States, 60141
        • Edward Hines Jr VA Hospital
      • Libertyville, Illinois, United States, 60048
        • Condell Memorial Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61636
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
      • Peoria, Illinois, United States, 61615
        • Illinois CancerCare-Peoria
      • Springfield, Illinois, United States, 62781
        • Springfield Memorial Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Indiana
      • Anderson, Indiana, United States, 46016
        • Ascension Saint Vincent Anderson
      • Fort Wayne, Indiana, United States, 46805
        • Parkview Hospital Randallia
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Regional Medical Center
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care
      • Muncie, Indiana, United States, 47303
        • IU Health Ball Memorial Hospital
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403
        • Mercy Hospital
      • Cedar Rapids, Iowa, United States, 52402
        • Saint Luke's Hospital
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center-Overland Park
      • Wichita, Kansas, United States, 67214
        • Ascension Via Christi Hospitals Wichita
      • Wichita, Kansas, United States, 67214
        • Wesley Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Luminis Health Anne Arundel Medical Center
      • Baltimore, Maryland, United States, 21237
        • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Baltimore, Maryland, United States, 21239
        • MedStar Good Samaritan Hospital
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
      • Columbia, Maryland, United States, 21044
        • Central Maryland Radiation Oncology in Howard County
      • Glen Burnie, Maryland, United States, 21061
        • UM Baltimore Washington Medical Center/Tate Cancer Center
      • Ocean Pines, Maryland, United States, 21811
        • TidalHealth Richard A Henson Cancer Institute
      • Salisbury, Maryland, United States, 21801
        • TidalHealth Peninsula Regional
      • Towson, Maryland, United States, 21204
        • UM Saint Joseph Medical Center
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital and Medical Center
      • Lowell, Massachusetts, United States, 01854
        • Lowell General Hospital
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center - University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
      • Bay City, Michigan, United States, 48706
        • McLaren Cancer Institute-Bay City
      • Brighton, Michigan, United States, 48114
        • Trinity Health Medical Center - Brighton
      • Brownstown, Michigan, United States, 48183
        • Henry Ford Cancer Institute-Downriver
      • Chelsea, Michigan, United States, 48118
        • Chelsea Hospital
      • Clarkston, Michigan, United States, 48346
        • McLaren Cancer Institute-Clarkston
      • Clarkston, Michigan, United States, 48346
        • Michigan Healthcare Professionals Clarkston
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb Hospital-Clinton Township
      • Dearborn, Michigan, United States, 48124
        • Corewell Health Dearborn Hospital
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Michigan Healthcare Professionals Farmington
      • Flint, Michigan, United States, 48532
        • McLaren Cancer Institute-Flint
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Lapeer, Michigan, United States, 48446
        • McLaren Cancer Institute-Lapeer Region
      • Livonia, Michigan, United States, 48154
        • Trinity Health Saint Mary Mercy Livonia Hospital
      • Macomb, Michigan, United States, 48044
        • Michigan Healthcare Professionals Macomb
      • Mount Clemens, Michigan, United States, 48043
        • McLaren Cancer Institute-Macomb
      • Mount Pleasant, Michigan, United States, 48858
        • McLaren Cancer Institute-Central Michigan
      • Muskegon, Michigan, United States, 49444
        • Trinity Health Muskegon Hospital
      • Owosso, Michigan, United States, 48867
        • McLaren Cancer Institute-Owosso
      • Petoskey, Michigan, United States, 49770
        • McLaren Cancer Institute-Northern Michigan
      • Pontiac, Michigan, United States, 48341
        • Trinity Health Saint Joseph Mercy Oakland Hospital
      • Port Huron, Michigan, United States, 48060
        • McLaren-Port Huron
      • Royal Oak, Michigan, United States, 48073
        • Corewell Health William Beaumont University Hospital
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Saint Joseph Hospital
      • Troy, Michigan, United States, 48098
        • Michigan Healthcare Professionals Troy
      • Troy, Michigan, United States, 48085
        • Corewell Health Beaumont Troy Hospital
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital
    • Minnesota
      • Albert Lea, Minnesota, United States, 56007
        • Mayo Clinic Health System in Albert Lea
      • Duluth, Minnesota, United States, 55805
        • Saint Luke's Hospital of Duluth
      • Mankato, Minnesota, United States, 56001
        • Mayo Clinic Health Systems-Mankato
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Northfield, Minnesota, United States, 55057
        • Mayo Clinic Radiation Therapy-Northfield
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • Joplin, Missouri, United States, 64804
        • Freeman Health System
      • Kansas City, Missouri, United States, 64154
        • University of Kansas Cancer Center - North
      • Kansas City, Missouri, United States, 64116
        • North Kansas City Hospital
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
      • North Kansas City, Missouri, United States, 64116
        • University of Kansas Cancer Center at North Kansas City Hospital
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • St Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • St Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Great Falls, Montana, United States, 59405
        • Benefis Sletten Cancer Institute
      • Missoula, Montana, United States, 59804
        • Community Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Dover, New Hampshire, United States, 03820
        • Wentworth-Douglass Hospital
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Englewood, New Jersey, United States, 07631
        • Englewood Hospital and Medical Center
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
      • Mount Holly, New Jersey, United States, 08060
        • Virtua Memorial
      • Voorhees Township, New Jersey, United States, 08043
        • Virtua Voorhees
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Bay Shore, New York, United States, 11706
        • Northwell Health Imbert Cancer Center
      • Brooklyn, New York, United States, 11215
        • New York-Presbyterian/Brooklyn Methodist Hospital
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • East White Plains, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • Elmira, New York, United States, 14905
        • Arnot Ogden Medical Center/Falck Cancer Center
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10075
        • Lenox Hill Hospital
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Staten Island, New York, United States, 10305
        • Staten Island University Hospital
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28210
        • Atrium Health Pineville/LCI-Pineville
      • Charlotte, North Carolina, United States, 28262
        • Atrium Health University City/LCI-University
      • Concord, North Carolina, United States, 28025
        • Atrium Health Cabarrus/LCI-Concord
      • Monroe, North Carolina, United States, 28112
        • Atrium Health Union/LCI-Union
      • Shelby, North Carolina, United States, 28150
        • Atrium Health Cleveland/LCI-Cleveland
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
    • Ohio
      • Akron, Ohio, United States, 44307
        • Cleveland Clinic Akron General
      • Akron, Ohio, United States, 44304
        • Summa Health System - Akron Campus
      • Chardon, Ohio, United States, 44024
        • Geauga Hospital
      • Chillicothe, Ohio, United States, 45601
        • Adena Regional Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44111
        • Cleveland Clinic Cancer Center/Fairview Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43222
        • Mount Carmel Health Center West
      • Dayton, Ohio, United States, 45415
        • Dayton Physician LLC - Englewood
      • Elyria, Ohio, United States, 44035
        • Mercy Cancer Center-Elyria
      • Independence, Ohio, United States, 44131
        • Cleveland Clinic Cancer Center Independence
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • Middleburg Heights, Ohio, United States, 44130
        • UH Seidman Cancer Center at Southwest General Hospital
      • Parma, Ohio, United States, 44129
        • University Hospitals Parma Medical Center
      • Strongsville, Ohio, United States, 44136
        • Cleveland Clinic Cancer Center Strongsville
      • Westlake, Ohio, United States, 44145
        • UHHS-Westlake Medical Center
      • Wooster, Ohio, United States, 44691
        • Cleveland Clinic Wooster Family Health and Surgery Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Jefferson Abington Hospital
      • Broomall, Pennsylvania, United States, 19008
        • Crozer-Keystone Regional Cancer Center at Broomall
      • Bryn Mawr, Pennsylvania, United States, 19010
        • Bryn Mawr Hospital
      • Chadds Ford, Pennsylvania, United States, 19317
        • Christiana Care Health System-Concord Health Center
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Dunmore, Pennsylvania, United States, 18512
        • Northeast Radiation Oncology Center
      • Gettysburg, Pennsylvania, United States, 17325
        • Adams Cancer Center
      • Glen Mills, Pennsylvania, United States, 19342
        • Crozer Regional Cancer Center at Brinton Lake
      • Lewisburg, Pennsylvania, United States, 17837
        • Geisinger Medical Oncology-Lewisburg
      • Media, Pennsylvania, United States, 19063
        • Riddle Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19114
        • Jefferson Torresdale Hospital
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Reading, Pennsylvania, United States, 19605
        • Penn State Health Saint Joseph Medical Center
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Medical Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Cancer Center
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • AnMed Health Cancer Center
      • Boiling Springs, South Carolina, United States, 29316
        • Prisma Health Cancer Institute - Spartanburg
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Faris
      • Greenville, South Carolina, United States, 29615
        • Prisma Health Cancer Institute - Eastside
      • Greenwood, South Carolina, United States, 29646
        • Self Regional Healthcare
      • Hilton Head Island, South Carolina, United States, 29926
        • The Radiation Oncology Center-Hilton Head/Bluffton
      • Lancaster, South Carolina, United States, 29720
        • Lancaster Radiation Therapy Center
      • Rock Hill, South Carolina, United States, 29730
        • Rock Hill Radiation Therapy Center
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Rapid City Regional Hospital
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Covenant Health Cancer Centers
      • Maryville, Tennessee, United States, 37804
        • Blount Memorial Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Galveston, Texas, United States, 77555-0565
        • University of Texas Medical Branch
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • League City, Texas, United States, 77573
        • UTMB Cancer Center at Victory Lakes
    • Utah
      • Ogden, Utah, United States, 84405
        • Ogden Regional Medical Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Vermont
      • Berlin Corners, Vermont, United States, 05602
        • Central Vermont Medical Center/National Life Cancer Treatment
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
      • Saint Johnsbury, Vermont, United States, 05819
        • Dartmouth Cancer Center - North
    • Virginia
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
      • Wheeling, West Virginia, United States, 26003
        • Wheeling Hospital/Schiffler Cancer Center
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Brookfield, Wisconsin, United States, 53045
        • Ascension Southeast Wisconsin Hospital - Elmbrook Campus
      • Eau Claire, Wisconsin, United States, 54701
        • Mayo Clinic Health System-Eau Claire Clinic
      • Eau Claire, Wisconsin, United States, 54703
        • Mayo Clinic Health System Eau Claire Hospital-Luther Campus
      • Franklin, Wisconsin, United States, 53132
        • Ascension Saint Francis - Reiman Cancer Center
      • Grafton, Wisconsin, United States, 53024
        • Aurora Cancer Care-Grafton
      • Green Bay, Wisconsin, United States, 54311
        • Aurora BayCare Medical Center
      • Johnson Creek, Wisconsin, United States, 53038
        • University of Wisconsin Carbone Cancer Center - Johnson Creek
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • La Crosse, Wisconsin, United States, 54601
        • Mayo Clinic Health System-Franciscan Healthcare
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Menomonee Falls, Wisconsin, United States, 53051
        • Froedtert Menomonee Falls Hospital
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Luke's Medical Center
      • Milwaukee, Wisconsin, United States, 53233
        • Aurora Sinai Medical Center
      • Oshkosh, Wisconsin, United States, 54904
        • Vince Lombardi Cancer Clinic - Oshkosh
      • Racine, Wisconsin, United States, 53405
        • Ascension All Saints Hospital
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Two Rivers, Wisconsin, United States, 54241
        • Vince Lombardi Cancer Clinic-Two Rivers
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer Center
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston
      • Wisconsin Rapids, Wisconsin, United States, 54494
        • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria [prior to Step 1 registration]:

  • 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.

    • 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:

    1. History/physical examination;
    2. 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);
    3. MRI of the brain with contrast or diagnostic head CT with contrast;
    4. 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.

      1. 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.
      2. 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

Inclusion Criteria [prior to Step 2 registration]:

  • 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.

Exclusion Criteria:

  • 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
  • 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;

      1. 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.
      2. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PCI using 3DCRT
Prophylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT) for 2 weeks, 5 fractions/week.
Radiation: Three-Dimensional Conformal Radiation Therapy
daily fractions
Other Names:
  • 3-dimensional conformal radiation therapy
  • 3-dimensional radiation therapy
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
  • 3DCRT
Experimental: PCI with HA using IMRT
PCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) for 2 weeks, 5 fractions/week.
Radiation: Intensity-Modulated Radiation Therapy
daily fractions
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)
Time Frame: Baseline and six months
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.
Baseline and six months
Number of Participants With Intracranial Relapse at 12 Months (Phase II)
Time Frame: From baseline to 12 months
Intracranial relapse, defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast.
From baseline to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Neurocognitive Failure (Phase III)
Time Frame: 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.
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.
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)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
Time Frame: Baseline, 3, 12 months.
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.
Baseline, 3, 12 months.
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
Time Frame: Baseline, 18, 24 months.
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.
Baseline, 18, 24 months.
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
Time Frame: Baseline, 18, 24 months.
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.
Baseline, 18, 24 months.
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
Time Frame: Baseline, 18, 24 months.
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.
Baseline, 18, 24 months.
Number of Participants With Deterioration in TMT Part B Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in TMT Part B Score (Phase III)
Time Frame: Baseline, 18, 24 months.

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.
Baseline, 18, 24 months.
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants by Highest Grade Adverse Event Reported (Phase III)
Time Frame: From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years.
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.
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)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
Time Frame: Baseline, 3, 6, 12 months.
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.
Baseline, 3, 6, 12 months.
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
Time Frame: Baseline,18, 24 months.
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.
Baseline,18, 24 months.
Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months
Time Frame: 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.
6 months
Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III)
Time Frame: Baseline to two years
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.
Baseline to two years
Overall Survival (Phase III)
Time Frame: 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.
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.
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)
Time Frame: 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.
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.
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)
Time Frame: Baseline to 6 months
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.
Baseline to 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III) by Sex
Time Frame: Baseline and six months
NIH-required analysis. 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.
Baseline and six months
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III) by Ethnicity
Time Frame: Baseline and six months
NIH-required analysis. 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.
Baseline and six months
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III) by Race
Time Frame: Baseline and six months
NIH-required analysis. 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.
Baseline and six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)
Radiation Therapy Oncology Group

Investigators

  • Principal Investigator: Vinai Gondi, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2015

Primary Completion (Actual)

May 18, 2023

Study Completion (Actual)

September 4, 2025

Study Registration Dates

First Submitted

December 16, 2015

First Submitted That Met QC Criteria

December 16, 2015

First Posted (Estimated)

December 18, 2015

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-CC003 (Other Identifier: DCP)
  • NCI-2015-01548 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • UG1CA189867 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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