AzTrials
AzTrials

Metastatic Lung Small Cell CarcinomaPhase 3NCT04804644

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

A Phase 3 study testing Biospecimen Collection, Magnetic Resonance Imaging and Memantine Hydrochloride in people with Metastatic Lung Small Cell Carcinoma and Metastatic Malignant Neoplasm in the Brain, run by NRG Oncology at 231 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Magnetic Resonance Imaging and Memantine Hydrochloride
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
152 participants
Where
231 sitesin 2 countries
Study dates
8 Jun 2021to 1 Jul 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

231 sites in 2 countries.

231 sites in 2 countries

United States227 sites

  • Saint Luke's Cancer Center - Allentown

    Allentown, Pennsylvania, 18104

  • UPMC Altoona

    Altoona, Pennsylvania, 16601

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Luminis Health Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • IU Health West Hospital

    Avon, Indiana, 46123

  • UH Seidman Cancer Center at UH Avon Health Center

    Avon, Ohio, 44011

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Luke's University Hospital-Bethlehem Campus

    Bethlehem, Pennsylvania, 18015

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Sands Cancer Center

    Canandaigua, New York, 14424

  • Northside Hospital-Cherokee

    Canton, Georgia, 30115

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Carlisle Regional Cancer Center

    Carlisle, Pennsylvania, 17015

  • IU Health North Hospital

    Carmel, Indiana, 46032

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Chambersburg Hospital

    Chambersburg, Pennsylvania, 17201

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • Central Maryland Radiation Oncology in Howard County

    Columbia, Maryland, 21044

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • MD Anderson in The Woodlands

    Conroe, Texas, 77384

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Minnesota Oncology - Coon Rapids

    Coon Rapids, Minnesota, 55433

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Northside Hospital-Forsyth

    Cumming, Georgia, 30041

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • University of Maryland Shore Medical Center at Easton

    Easton, Maryland, 21601

  • Saint Luke's Hospital-Anderson Campus

    Easton, Pennsylvania, 18045

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Minnesota Oncology - Edina

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Ephrata Cancer Center

    Ephrata, Pennsylvania, 17522

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Saint Vincent Hospital

    Erie, Pennsylvania, 16544

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • UPMC Cancer Center at UPMC Horizon

    Farrell, Pennsylvania, 16121

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • UM Baltimore Washington Medical Center/Tate Cancer Center

    Glen Burnie, Maryland, 21061

  • Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Smilow Cancer Hospital Care Center at Greenwich

    Greenwich, Connecticut, 06830

  • Self Regional Healthcare

    Greenwood, South Carolina, 29646

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • UPMC Pinnacle Cancer Center/Community Osteopathic Campus

    Harrisburg, Pennsylvania, 17109

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • MD Anderson West Houston

    Houston, Texas, 77079

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • IU Health Methodist Hospital

    Indianapolis, Indiana, 46202

  • Freeman Health System

    Joplin, Missouri, 64804

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

  • McLaren Cancer Institute-Lapeer Region

    Lapeer, Michigan, 48446

  • UT MD Anderson - League City

    League City, Texas, 77573

  • Sechler Family Cancer Center

    Lebanon, Pennsylvania, 17042

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Geisinger Medical Oncology-Lewisburg

    Lewisburg, Pennsylvania, 17837

  • Baptist Health Lexington

    Lexington, Kentucky, 40503

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • UofL Health Medical Center Northeast

    Louisville, Kentucky, 40245

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Fairview Clinics and Surgery Center Maple Grove

    Maple Grove, Minnesota, 55369

  • Minnesota Oncology - Maple Grove

    Maple Grove, Minnesota, 55369

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint Mary's Oncology/Hematology Associates of Marlette

    Marlette, Michigan, 48453

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • UPMC Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • Monticello Cancer Center

    Monticello, Minnesota, 55362

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • Northern Westchester Hospital

    Mount Kisco, New York, 10549

  • McLaren Cancer Institute-Central Michigan

    Mount Pleasant, Michigan, 48858

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • HSHS Saint Elizabeth's Hospital

    O'Fallon, Illinois, 62269

  • Drexel Town Square Health Center

    Oak Creek, Wisconsin, 53154

  • TidalHealth Richard A Henson Cancer Institute

    Ocean Pines, Maryland, 21811

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Kaiser Permanente-Ontario

    Ontario, California, 91761

  • Upstate Cancer Center Radiation Oncology at Oswego

    Oswego, New York, 13126

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Mercy Health - Perrysburg Hospital

    Perrysburg, Ohio, 43551

  • McLaren Cancer Institute-Northern Michigan

    Petoskey, Michigan, 49770

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Jefferson Torresdale Hospital

    Philadelphia, Pennsylvania, 19114

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC-Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC-Presbyterian Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC-Saint Margaret

    Pittsburgh, Pennsylvania, 15215

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UPMC-Saint Clair Hospital Cancer Center

    Pittsburgh, Pennsylvania, 15243

  • McLaren-Port Huron

    Port Huron, Michigan, 48060

  • Saint Luke's Hospital - Upper Bucks Campus

    Quakertown, Pennsylvania, 18951

  • Saint Luke's Hospital-Quakertown Campus

    Quakertown, Pennsylvania, 18951

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Aspirus Cancer Care - James Beck Cancer Center

    Rhinelander, Wisconsin, 54501

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Wilmot Cancer Institute Radiation Oncology at Greece

    Rochester, New York, 14606

  • University of Rochester

    Rochester, New York, 14642

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Sainte Genevieve County Memorial Hospital

    Sainte Genevieve, Missouri, 63670

  • TidalHealth Peninsula Regional

    Salisbury, Maryland, 21801

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Sanford Cancer Center Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Aspirus Cancer Care - Stevens Point

    Stevens Point, Wisconsin, 54481

  • Lakeview Hospital

    Stillwater, Minnesota, 55082

  • Saint Luke's Hospital - Monroe Campus

    Stroudsburg, Pennsylvania, 18360

  • MD Anderson in Sugar Land

    Sugar Land, Texas, 77478

  • Missouri Baptist Sullivan Hospital

    Sullivan, Missouri, 63080

  • BJC Outpatient Center at Sunset Hills

    Sunset Hills, Missouri, 63127

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Upstate Cancer Center at Hill Radiation Oncology

    Syracuse, New York, 13210

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center - McKinley Campus

    Tampa, Florida, 33612

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • MyMichigan Medical Center Tawas

    Tawas City, Michigan, 48764

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Mercy Health - Saint Anne Hospital

    Toledo, Ohio, 43623

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • SMC Center for Hematology Oncology Union

    Union, South Carolina, 29379

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The Carle Foundation Hospital

    Urbana, Illinois, 61801

  • Upstate Cancer Center at Verona

    Verona, New York, 13478

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

  • Aspirus Regional Cancer Center

    Wausau, Wisconsin, 54401

  • Wilmot Cancer Institute at Webster

    Webster, New York, 14580

  • Moffitt Cancer Center at Wesley Chapel

    Wesley Chapel, Florida, 33544

  • Froedtert West Bend Hospital/Kraemer Cancer Center

    West Bend, Wisconsin, 53095

  • Saint Mary's Oncology/Hematology Associates of West Branch

    West Branch, Michigan, 48661

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Geisinger Wyoming Valley/Henry Cancer Center

    Wilkes-Barre, Pennsylvania, 18711

  • Divine Providence Hospital

    Williamsport, Pennsylvania, 17754

  • Christiana Care Health System-Wilmington Hospital

    Wilmington, Delaware, 19801

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • Minnesota Oncology Hematology PA-Woodbury

    Woodbury, Minnesota, 55125

  • WellSpan Health-York Cancer Center

    York, Pennsylvania, 17403

  • WellSpan Health-York Hospital

    York, Pennsylvania, 17403

  • UPMC Memorial

    York, Pennsylvania, 17408

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

Other trials in United States

Canada4 sites

  • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)

    Québec, Quebec, G1R 2J6

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

  1. 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.

Being tested
Biospecimen Collection, Magnetic Resonance Imaging, Memantine Hydrochloride, Neurocognitive Assessment, Stereotactic Radiosurgery
Medical subject headings
Small Cell Lung Carcinoma, Brain Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Memantine HydrochlorideDrug

    Also called Ebixia, Namenda

    Given PO

  • Neurocognitive AssessmentOther

    Ancillary studies

  • Stereotactic RadiosurgeryRadiation

    Also called SRS, Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy

    Undergo SRS

  • Survey AdministrationOther

    Ancillary studies

  • Whole-Brain RadiotherapyRadiation

    Also called WBRT, whole-brain radiation therapy

    Undergo HA-WBRT

Study groups in NCT04804644
Study groupRoleWhat they receive
Arm I (SRS)ExperimentalPatients undergo SRS over 1 day (in some cases several days). Patients undergo blood sample collection and MRI throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Neurocognitive Assessment; Radiation: Stereotactic Radiosurgery; Other: Survey Administration
Arm II (HA-WBRT, memantine)Active comparatorPatients 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.
Receives: Procedure: Magnetic Resonance Imaging; Drug: Memantine Hydrochloride; Other: Neurocognitive Assessment; Other: Survey Administration; Radiation: Whole-Brain Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to neurocognitive failure

    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.

    Measured: Up to 1 year

Secondary outcomes (9)

  1. Preservation of neurocognitive function

    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.

    Measured: 1 year

  2. Perceived difficulties in cognition

    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).

    Measured: Up to 1 year

  3. Symptom burden

    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.

    Measured: Up to 1 year

  4. Time to intracranial disease progression

    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.

    Measured: From the date of randomization to the date of intracranial disease progression, assessed up to 10 years

  5. Overall survival

    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.

    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, assessed up to 10 years

  6. Time to neurologic death

    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.

    Measured: From the date of randomization to the date of neurologic death, assessed up to 10 years

  7. Salvage procedures used to manage recurrent intracranial disease

    Will be described by each arm.

    Measured: Up to 10 years

  8. Incidence of adverse events

    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.

    Measured: Up to 10 years

  9. Development of cerebral necrosis

    Measured: Up to 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2021
  2. Study start8 Jun 2021
  3. Primary completion24 Jun 2026
  4. Study completion1 Jul 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
152 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04804644
Sponsor's protocol ID
NRG-CC009
Other IDs
NCI-2020-11651, NRG-CC009, NRG-CC009, NRG-CC009, UG1CA189867
Status last verified
Aug 2026
First submitted
9 Mar 2021
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Magnetic Resonance Imaging and Memantine Hydrochloride in people with Metastatic Lung Small Cell Carcinoma and Metastatic Malignant Neoplasm in the Brain, run by NRG Oncology at 231 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 231 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to neurocognitive failure (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04804644.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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