Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability

September 9, 2026 updated by: NRG Oncology

Phase III Trial of Stereotactic Radiosurgery (SRS) Versus Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for Brain Metastases From Small Cell Lung Cancer

This phase III trial compares the effect of stereotactic radiosurgery to standard of care memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of the brain) for the treatment of small cell lung cancer that has spread to the brain. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole brain radiation therapy delivers a low dose of radiation to the entire brain including the normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT) decreases the amount of radiation that is delivered to the hippocampus which is a brain structure that is important for memory. The drug, memantine, is also often given with whole brain radiotherapy because it may decrease the risk of side effects related to thinking and memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking compared to standard of care HA-WBRT plus memantine.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

I. Determine whether stereotactic radiosurgery (SRS) relative to whole brain radiotherapy with hippocampal avoidance (HA-WBRT) plus memantine hydrochloride (memantine) for brain metastases from small cell lung cancer (SCLC) prevents cognitive function failure as measured by cognitive decline on a battery of tests: the Hopkins Verbal Learning Test - Revised (HVLT-R), Controlled Oral Word Association (COWA) test, and the Trail Making Test (TMT).

SECONDARY OBJECTIVES:

I. Determine whether SRS relative to HA-WBRT plus memantine for brain metastases from SCLC preserves cognitive function as separately measured by the HVLT-R, COWA, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP).

II. Assess perceived difficulties in cognitive abilities using Patient Reported Outcomes Measurement Information System (PROMIS) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

III. Assess symptom burden using the MD Anderson Symptom Inventory for brain tumor (MDASI-BT) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

IV. Compare cumulative incidence of intracranial disease progression after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

V. Compare overall survival after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

VI. Compare cumulative incidence of neurologic death after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

VII. Compare the number of salvage procedures used to manage recurrent intracranial disease following SRS relative to HA-WBRT plus memantine for SCLC brain metastases.

VIII. Compare adverse events between the treatment arms according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 criteria.

IX. Compare the risk of developing cerebral necrosis between SRS and HA-WBRT plus memantine in patients receiving concurrent immunotherapy.

EXPLORATORY OBJECTIVES:

I. Compare cumulative incidence of local brain recurrence, distant brain relapse, and leptomeningeal dissemination after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

II. Compare the cost of brain-related therapies and quality-adjusted life years in patients who receive SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

III. Evaluate the time delay to salvage WBRT or HA-WBRT in patients enrolled on the SRS arm.

IV. Evaluate whether a time delay for chemotherapy has an effect on overall survival in patients receiving HA WBRT plus memantine relative to SRS for brain metastases from SCLC.

V. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.

VI. Evaluate the correlation between neurocognitive functioning and patient-reported outcomes.

VII. Collect serum, plasma and imaging studies for future translational research analyses.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SRS over 1 day (in some cases several days).

ARM II: Patients undergo HA-WBRT once daily (QD) for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive memantine orally (PO) QD or twice daily (BID) for up to 24 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection and magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patients are followed up every 2-3 months for 1 year, and then every 6 months thereafter.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
152

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network-Princess Margaret Hospital
    • Quebec
      • Québec, Quebec, Canada, G1R 2J6
        • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital in Arizona
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Ontario, California, United States, 91761
        • Kaiser Permanente-Ontario
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
    • Connecticut
      • Greenwich, Connecticut, United States, 06830
        • Smilow Cancer Hospital Care Center at Greenwich
      • Guilford, Connecticut, United States, 06437
        • Smilow Cancer Hospital Care Center - Guilford
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Center/Yale-New Haven Hospital
      • Trumbull, Connecticut, United States, 06611
        • Smilow Cancer Hospital Care Center-Trumbull
      • Waterford, Connecticut, United States, 06385
        • Smilow Cancer Hospital Care Center - Waterford
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Beebe Medical Center
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
      • Newark, Delaware, United States, 19713
        • Delaware Clinical and Laboratory Physicians PA
      • Newark, Delaware, United States, 19713
        • Medical Oncology Hematology Consultants PA
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
      • Rehoboth Beach, Delaware, United States, 19971
        • Beebe Health Campus
      • Wilmington, Delaware, United States, 19801
        • Christiana Care Health System-Wilmington Hospital
    • Florida
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Gainesville, Florida, United States, 32610
        • UF Health Cancer Institute - Gainesville
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
      • Tampa, Florida, United States, 33607
        • Moffitt Cancer Center-International Plaza
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center - McKinley Campus
      • Wesley Chapel, Florida, United States, 33544
        • Moffitt Cancer Center at Wesley Chapel
    • 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, 30342
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Canton, Georgia, United States, 30115
        • Northside Hospital-Cherokee
      • Cumming, Georgia, United States, 30041
        • Northside Hospital-Forsyth
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Rush-Copley Medical Center
      • Centralia, Illinois, United States, 62801
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • Rush MD Anderson Cancer Center
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • DeKalb, Illinois, United States, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • O'Fallon, Illinois, United States, 62269
        • HSHS Saint Elizabeth's Hospital
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Urbana, Illinois, United States, 61801
        • The Carle Foundation Hospital
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Indiana
      • Avon, Indiana, United States, 46123
        • IU Health West Hospital
      • Carmel, Indiana, United States, 46032
        • IU Health North Hospital
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • IU Health Methodist Hospital
    • Iowa
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Ames, Iowa, United States, 50010
        • McFarland Clinic - Ames
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Baptist Health Lexington
      • Louisville, Kentucky, United States, 40202
        • The James Graham Brown Cancer Center at University of Louisville
      • Louisville, Kentucky, United States, 40245
        • UofL Health Medical Center Northeast
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Mary Bird Perkins Cancer Center
    • 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, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
      • Columbia, Maryland, United States, 21044
        • Central Maryland Radiation Oncology in Howard County
      • Easton, Maryland, United States, 21601
        • University of Maryland Shore Medical Center at Easton
      • 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
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • 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 IHA Medical Group Hematology Oncology - Brighton
      • Brighton, Michigan, United States, 48114
        • Trinity Health Medical Center - Brighton
      • Canton, Michigan, United States, 48188
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
      • Canton, Michigan, United States, 48188
        • Trinity Health Medical Center - Canton
      • Caro, Michigan, United States, 48723
        • Caro Cancer Center
      • Chelsea, Michigan, United States, 48118
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
      • Chelsea, Michigan, United States, 48118
        • Chelsea Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Flint, Michigan, United States, 48532
        • McLaren Cancer Institute-Flint
      • Lansing, Michigan, United States, 48910
        • Karmanos Cancer Institute at McLaren Greater Lansing
      • Lapeer, Michigan, United States, 48446
        • McLaren Cancer Institute-Lapeer Region
      • Livonia, Michigan, United States, 48154
        • Trinity Health Saint Mary Mercy Livonia Hospital
      • Marlette, Michigan, United States, 48453
        • Saint Mary's Oncology/Hematology Associates of Marlette
      • Mount Clemens, Michigan, United States, 48043
        • McLaren Cancer Institute-Macomb
      • Mount Pleasant, Michigan, United States, 48858
        • McLaren Cancer Institute-Central Michigan
      • Petoskey, Michigan, United States, 49770
        • McLaren Cancer Institute-Northern Michigan
      • Port Huron, Michigan, United States, 48060
        • McLaren-Port Huron
      • Saginaw, Michigan, United States, 48604
        • Oncology Hematology Associates of Saginaw Valley PC
      • Saginaw, Michigan, United States, 48601
        • MyMichigan Medical Center Saginaw
      • Tawas City, Michigan, United States, 48764
        • MyMichigan Medical Center Tawas
      • West Branch, Michigan, United States, 48661
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48197
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
        • Sanford Joe Lueken Cancer Center
      • Burnsville, Minnesota, United States, 55337
        • Minnesota Oncology - Burnsville
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Coon Rapids, Minnesota, United States, 55433
        • Minnesota Oncology - Coon Rapids
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Edina, Minnesota, United States, 55435
        • Minnesota Oncology - Edina
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Maple Grove, Minnesota, United States, 55369
        • Fairview Clinics and Surgery Center Maple Grove
      • Maple Grove, Minnesota, United States, 55369
        • Minnesota Oncology - Maple Grove
      • Maplewood, Minnesota, United States, 55109
        • Minnesota Oncology Hematology PA-Maplewood
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Monticello, Minnesota, United States, 55362
        • Monticello Cancer Center
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Stillwater, Minnesota, United States, 55082
        • Lakeview Hospital
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology Hematology PA-Woodbury
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Joplin, Missouri, United States, 64804
        • Freeman Health System
      • Sainte Genevieve, Missouri, United States, 63670
        • Sainte Genevieve County Memorial Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
      • St Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Sullivan, Missouri, United States, 63080
        • Missouri Baptist Sullivan Hospital
      • Sunset Hills, Missouri, United States, 63127
        • BJC Outpatient Center at Sunset Hills
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Great Falls, Montana, United States, 59405
        • Benefis Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Logan Health Medical Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper Hospital University Medical Center
    • New York
      • Canandaigua, New York, United States, 14424
        • Sands Cancer Center
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • Mount Kisco, New York, United States, 10549
        • Northern Westchester Hospital
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • Oswego, New York, United States, 13126
        • Upstate Cancer Center Radiation Oncology at Oswego
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Rochester, New York, United States, 14606
        • Wilmot Cancer Institute Radiation Oncology at Greece
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • Syracuse, New York, United States, 13210
        • Upstate Cancer Center at Hill Radiation Oncology
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • Verona, New York, United States, 13478
        • Upstate Cancer Center at Verona
      • Webster, New York, United States, 14580
        • Wilmot Cancer Institute at Webster
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Avon, Ohio, United States, 44011
        • UH Seidman Cancer Center at UH Avon Health Center
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43215
        • Grant Medical Center
      • Delaware, Ohio, United States, 43015
        • Delaware Health Center-Grady Cancer Center
      • Delaware, Ohio, United States, 43015
        • Grady Memorial Hospital
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • Perrysburg, Ohio, United States, 43551
        • Mercy Health - Perrysburg Hospital
      • Toledo, Ohio, United States, 43623
        • Mercy Health - Saint Anne Hospital
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18104
        • Saint Luke's Cancer Center - Allentown
      • Altoona, Pennsylvania, United States, 16601
        • UPMC Altoona
      • Beaver, Pennsylvania, United States, 15009
        • UPMC-Heritage Valley Health System Beaver
      • Bethlehem, Pennsylvania, United States, 18015
        • Saint Luke's University Hospital-Bethlehem Campus
      • Carlisle, Pennsylvania, United States, 17015
        • Carlisle Regional Cancer Center
      • Chadds Ford, Pennsylvania, United States, 19317
        • Christiana Care Health System-Concord Health Center
      • Chambersburg, Pennsylvania, United States, 17201
        • Chambersburg Hospital
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Easton, Pennsylvania, United States, 18045
        • Saint Luke's Hospital-Anderson Campus
      • Ephrata, Pennsylvania, United States, 17522
        • Ephrata Cancer Center
      • Erie, Pennsylvania, United States, 16505
        • UPMC Hillman Cancer Center Erie
      • Erie, Pennsylvania, United States, 16544
        • Saint Vincent Hospital
      • Farrell, Pennsylvania, United States, 16121
        • UPMC Cancer Center at UPMC Horizon
      • Gettysburg, Pennsylvania, United States, 17325
        • Adams Cancer Center
      • Greensburg, Pennsylvania, United States, 15601
        • UPMC Cancer Centers - Arnold Palmer Pavilion
      • Harrisburg, Pennsylvania, United States, 17109
        • UPMC Pinnacle Cancer Center/Community Osteopathic Campus
      • Lebanon, Pennsylvania, United States, 17042
        • Sechler Family Cancer Center
      • Lewisburg, Pennsylvania, United States, 17837
        • Geisinger Medical Oncology-Lewisburg
      • Monroeville, Pennsylvania, United States, 15146
        • UPMC Cancer Center - Monroeville
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19114
        • Jefferson Torresdale Hospital
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Magee Womens Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC-Shadyside Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Presbyterian Hospital
      • Pittsburgh, Pennsylvania, United States, 15215
        • UPMC-Saint Margaret
      • Pittsburgh, Pennsylvania, United States, 15237
        • UPMC-Passavant Hospital
      • Pittsburgh, Pennsylvania, United States, 15243
        • UPMC-Saint Clair Hospital Cancer Center
      • Quakertown, Pennsylvania, United States, 18951
        • Saint Luke's Hospital-Quakertown Campus
      • Quakertown, Pennsylvania, United States, 18951
        • Saint Luke's Hospital - Upper Bucks Campus
      • Stroudsburg, Pennsylvania, United States, 18360
        • Saint Luke's Hospital - Monroe Campus
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
      • Williamsport, Pennsylvania, United States, 17754
        • Divine Providence Hospital
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Cancer Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Hospital
      • York, Pennsylvania, United States, 17408
        • UPMC Memorial
    • South Carolina
      • Florence, South Carolina, United States, 29506
        • McLeod Regional Medical Center
      • Gaffney, South Carolina, United States, 29341
        • Gibbs Cancer Center-Gaffney
      • Greenwood, South Carolina, United States, 29646
        • Self Regional Healthcare
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
      • Union, South Carolina, United States, 29379
        • SMC Center for Hematology Oncology Union
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
    • Texas
      • Conroe, Texas, United States, 77384
        • MD Anderson in The Woodlands
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center
      • Houston, Texas, United States, 77079
        • MD Anderson West Houston
      • League City, Texas, United States, 77573
        • UT MD Anderson - League City
      • Sugar Land, Texas, United States, 77478
        • MD Anderson in Sugar Land
    • Virginia
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Madison, Wisconsin, United States, 53718
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
      • Menomonee Falls, Wisconsin, United States, 53051
        • Froedtert Menomonee Falls Hospital
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • New Richmond, Wisconsin, United States, 54017
        • Cancer Center of Western Wisconsin
      • Oak Creek, Wisconsin, United States, 53154
        • Drexel Town Square Health Center
      • Rhinelander, Wisconsin, United States, 54501
        • Aspirus Cancer Care - James Beck Cancer Center
      • Stevens Point, Wisconsin, United States, 54481
        • Aspirus Cancer Care - Stevens Point
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer Center
      • West Bend, Wisconsin, United States, 53095
        • Froedtert West Bend Hospital/Kraemer Cancer Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of small cell lung cancer within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic or brain metastasis);

    • Patients with de novo or recurrent small cell lung cancer are permitted.

  • Brain metastases =< 4 cm in largest diameter and outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior to study entry.

    • The total tumor volume must be 30 cm^3 or less. Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumor volume.
    • Brain metastases can be diagnosed synchronous to the initial diagnosis of small cell lung cancer or metachronous to the initial diagnosis and management of small cell lung cancer.

    • Brain metastases must be diagnosed on MRI, which will include the following elements:

      • REQUIRED MRI ELEMENTS

        • Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm.
        • Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged).
        • A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required. This can be acquired as a two dimensional (2D) or 3D image. If 2D, the images should be obtained in the axial plane.

      • ADDITIONAL RECOMMENDATIONS

        • Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence.
        • Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1.
        • Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.
        • Recommendation is that the study participants be scanned on the same MRI instrument at each time point.
        • Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020.
        • If additional sequences are obtained, total imaging time should not exceed 60 minutes.
        • If additional metastases not known at the time of registration/randomization or seen in the MRI used for eligibility are subsequently found on the radiation therapy (RT) planning MRI such that the total intacranial volume exceeds 30 cm^3, the patient is still considered eligible.
  • History/physical examination
  • Age >= 18
  • Karnofsky performance status of >= 70
  • Creatinine clearance >= 30 ml/min

  • Following the diagnosis of brain metastases, patients can initiate and treat with systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain metastases are asymptomatic and not located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment, brain MRI must be repeated to confirm eligibility.

    • Patients with symptomatic brain metastases and/or brain metastases in eloquent locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible for enrollment on the trial; however, the specific treatment approach of starting with systemic therapy alone and delaying brain radiation is not recommended for these patients.
  • Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
  • Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to registration. Women of childbearing potential and men who are sexually active must use contraception while on study.
  • Patients may have had prior intracranial surgical resection.
  • Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian.

  • The patient must provide study-specific informed consent prior to study entry.

    • Patients with impaired decision-making capacity are not permitted on study.
  • ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION

  • The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.

    • NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.
  • PRIOR TO STEP 2 REGISTRATION: The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.

NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.

Exclusion Criteria:

  • Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is permitted.

    • For patients receiving fractionated SRS on an every-other-day basis, planned infusion of cytotoxic chemotherapy is not permitted between SRS treatments.
  • Brainstem metastasis > 10 cm^3
  • Prior allergic reaction to memantine.
  • Patients with definitive leptomeningeal metastases.
  • Known history of demyelinating disease such as multiple sclerosis.
  • Contraindication to MR imaging such as implanted metal devices that are MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions regarding MRI compatibility of implanted objects should be reviewed with the Radiology Department performing the MRI).
  • Current use of (other N-methyl-D-aspartate [NMDA] antagonists) amantadine, ketamine, or dextromethorphan.

  • Radiographic evidence of hydrocephalus or other architectural change of the ventricular system resulting in significant anatomic distortion of the hippocampus, including placement of external ventricular drain or ventriculoperitoneal shunt.

    • Mild cases of hydrocephalus not resulting in significant anatomic distortion of the hippocampus are permitted.
  • Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial irradiation (PCI).

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm I (SRS)
Patients undergo SRS over 1 day (in some cases several days). Patients undergo blood sample collection and MRI throughout the study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Survey Administration
Ancillary studies
Radiation: Stereotactic Radiosurgery
Undergo SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • SRS
Other: Neurocognitive Assessment
Ancillary studies
Active Comparator: Arm II (HA-WBRT, memantine)
Patients also undergo HA-WBRT QD for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients will also receive memantine PO QD or BID for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Other: Survey Administration
Ancillary studies
Drug: Memantine Hydrochloride
Given PO
Other Names:
  • Namenda
  • Ebixia
Radiation: Whole-Brain Radiotherapy
Undergo HA-WBRT
Other Names:
  • WBRT
  • whole-brain radiation therapy
Other: Neurocognitive Assessment
Ancillary studies

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to neurocognitive failure
Time Frame: Up to 1 year
A failure is defined using the reliable change index (RCI) criteria, as measured by the Hopkins Verbal Learning Test - Revised (HVLT-R), Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) Parts A and B. The cumulative incidence approach will be used to estimate the percentage of failures while accounting for the competing risk of death.
Up to 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Preservation of neurocognitive function
Time Frame: 1 year
Neurocognitive function will be measured by the HVLT-R, COWA, and TMT. The HVLT-R has 3 parts that will be analyzed separately: Total Recall, Delayed Recall, and Delayed Recognition. The TMT also has 2 parts that will be analyzed separately: TMT Part A and TMT Part B. The COWA has a single outcome measure that will be analyzed. Standardized scores that adjust for age, education, and sex when necessary will be analyzed.
1 year
Perceived difficulties in cognition
Time Frame: Up to 1 year
Measured by Patient Reported Outcomes Measurement Information System (PROMIS). The total raw score for a PROMIS short form would be the sum of the values of the response to each question (therefore, for a short form which all questions are answered, the lowest possible score is 4 and the highest possible raw score is 20).
Up to 1 year
Symptom burden
Time Frame: Up to 1 year
Measured by MD Anderson Symptom Inventory for brain tumor (MDASI-BT). Four subscales (symptom severity, symptom interference, neurologic factor, and cognitive factor score) as well as certain individual items (fatigue, neurologic factor items, and cognitive factor items) of the MDASI-BT will be analyzed.
Up to 1 year
Time to intracranial disease progression
Time Frame: From the date of randomization to the date of intracranial disease progression, assessed up to 10 years
Time to any intracranial progression will be measured from the date of randomization to the date of intracranial disease progression. Death without an event will be treated as a competing risk. Alive patients without an event will be censored at their last known follow-up time. The percentage of patients with a failure will be determined using cumulative incidence.
From the date of randomization to the date of intracranial disease progression, assessed up to 10 years
Overall survival
Time Frame: From the date of randomization to the date of death, or otherwise, the last follow-up date on which the patient was reported alive, assessed up to 10 years
Overall survival will be measured from the date of randomization to the date of death, or, otherwise, the last follow-up date on which the patient was reported alive. The Kaplan-Meier method (Kaplan 1958) will be used to calculate the percentage of patients alive.
From the date of randomization to the date of death, or otherwise, the last follow-up date on which the patient was reported alive, assessed up to 10 years
Time to neurologic death
Time Frame: From the date of randomization to the date of neurologic death, assessed up to 10 years
Time to neurologic death will be measured from the date of randomization to the date of neurologic death. Death without an event will be treated as a competing risk. Alive patients without an event will be censored at their last known follow-up time. The percentage of patients with a failure will be determined using cumulative incidence.
From the date of randomization to the date of neurologic death, assessed up to 10 years
Salvage procedures used to manage recurrent intracranial disease
Time Frame: Up to 10 years
Will be described by each arm.
Up to 10 years
Incidence of adverse events
Time Frame: Up to 10 years
Graded by Common Terminology Criteria for Adverse Events version 5.0. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm.
Up to 10 years
Development of cerebral necrosis
Time Frame: Up to 10 years
Up to 10 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Estimates of treatment effect by sex
Time Frame: Up to 10 years
Estimates of the primary outcome treatment effect and the corresponding 95% confidence intervals (CIs) by sex.
Up to 10 years
Estimates of treatment effect by race
Time Frame: Up to 10 years
Estimates of the primary outcome treatment effect and the corresponding 95% CIs by race.
Up to 10 years
Estimates of treatment effect by ethnicity
Time Frame: Up to 10 years
Estimates of the primary outcome treatment effect and the corresponding 95% CIs by ethnicity.
Up to 10 years
White matter injury and hippocampal volume
Time Frame: 6 months
6 months
Time to local brain recurrence (in brain lesions present at trial enrollment and treated with either stereotactic radiosurgery [SRS] or hippocampal-avoidant whole brain radiotherapy [HA-WBRT])
Time Frame: Up to 10 years
Up to 10 years
Time to incidence of distant brain relapses
Time Frame: Up to 10 years
Up to 10 years
Time to leptomeningeal dissemination
Time Frame: Up to 10 years
Up to 10 years
Time delay to salvage WBRT or HA-WBRT in patients on the SRS arm
Time Frame: Baseline to first salvage treatment, assessed up to 10 years
Baseline to first salvage treatment, assessed up to 10 years
Cost and quality adjusted survival
Time Frame: Up to 1 year
Measured using the European Quality of Life Five Dimension Five Level Scale Questionnaire.
Up to 1 year
Correlation between neurocognitive function and patient-reported outcomes
Time Frame: Up to 1 year
Up to 1 year

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NRG Oncology

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vinai Gondi, NRG Oncology

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 8, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 24, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 9, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NRG-CC009 (Other Identifier: CTEP)
  • UG1CA189867 (U.S. NIH Grant/Contract)
  • NCI-2020-11651 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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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