Phase III Trial of Stereotactic Radiosurgery (SRS) Versus Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for Brain Metastases From Small Cell Lung Cancer
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. 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.
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.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugMemantine Hydrochloride
Given PO
- OtherNeurocognitive Assessment
Ancillary studies
- RadiationStereotactic Radiosurgery
Undergo SRS
- OtherSurvey Administration
Ancillary studies
- RadiationWhole-Brain Radiotherapy
Undergo HA-WBRT
Outcome measures
Primary
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.
Time frame: Up to 1 year
Secondary
Preservation of neurocognitive function
Time frame: 1 year
Perceived difficulties in cognition
Time frame: Up to 1 year
Symptom burden
Time frame: 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
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
Time to neurologic death
Time frame: 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
Incidence of adverse events
Time frame: Up to 10 years
Development of cerebral necrosis
Time frame: Up to 10 years
Eligibility criteria
Study locations (223)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Kaiser Permanente-Anaheim
Anaheim, California, 92806
Kaiser Permanente-Bellflower
Bellflower, California, 90706
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
Kaiser Permanente-Ontario
Ontario, California, 91761
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Yale University
New Haven, Connecticut, 06520
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385
Beebe Medical Center
Lewes, Delaware, 19958
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
Beebe Health Campus
Rehoboth Beach, Delaware, 19971
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, 19801
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612
Moffitt Cancer Center
Tampa, Florida, 33612
Moffitt Cancer Center at Wesley Chapel
Wesley Chapel, Florida, 33544
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
Northside Hospital-Cherokee
Canton, Georgia, 30115
Northside Hospital-Forsyth
Cumming, Georgia, 30041
Memorial Health University Medical Center
Savannah, Georgia, 31404
Rush-Copley Medical Center
Aurora, Illinois, 60504
Centralia Oncology Clinic
Centralia, Illinois, 62801
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Carle at The Riverfront
Danville, Illinois, 61832
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Carle Cancer Center
Urbana, Illinois, 61801
The Carle Foundation Hospital
Urbana, Illinois, 61801
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
IU Health West Hospital
Avon, Indiana, 46123
IU Health North Hospital
Carmel, Indiana, 46032
Goshen Center for Cancer Care
Goshen, Indiana, 46526
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
IU Health Methodist Hospital
Indianapolis, Indiana, 46202
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
Baptist Health Lexington
Lexington, Kentucky, 40503
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
Luminis Health Anne Arundel Medical Center
Annapolis, Maryland, 21401
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland, 21044
University of Maryland Shore Medical Center at Easton
Easton, Maryland, 21601
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland, 21061
TidalHealth Richard A Henson Cancer Institute
Ocean Pines, Maryland, 21811
TidalHealth Peninsula Regional
Salisbury, Maryland, 21801
Boston Medical Center
Boston, Massachusetts, 02118
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Caro Cancer Center
Caro, Michigan, 48723
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
McLaren Cancer Institute-Flint
Flint, Michigan, 48532
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, 48910
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Saint Mary's Oncology/Hematology Associates of Marlette
Marlette, Michigan, 48453
McLaren Cancer Institute-Macomb
Mount Clemens, Michigan, 48043
McLaren Cancer Institute-Central Michigan
Mount Pleasant, Michigan, 48858
McLaren Cancer Institute-Northern Michigan
Petoskey, Michigan, 49770
McLaren-Port Huron
Port Huron, Michigan, 48060
MyMichigan Medical Center Saginaw
Saginaw, Michigan, 48601
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, 48604
MyMichigan Medical Center Tawas
Tawas City, Michigan, 48764
Saint Mary's Oncology/Hematology Associates of West Branch
West Branch, Michigan, 48661
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Mercy Hospital
Coon Rapids, Minnesota, 55433
Fairview Southdale Hospital
Edina, Minnesota, 55435
Unity Hospital
Fridley, Minnesota, 55432
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Monticello Cancer Center
Monticello, Minnesota, 55362
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Lakeview Hospital
Stillwater, Minnesota, 55082
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Freeman Health System
Joplin, Missouri, 64804
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670
Mercy Hospital Springfield
Springfield, Missouri, 65804
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, 63127
Billings Clinic Cancer Center
Billings, Montana, 59101
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Logan Health Medical Center
Kalispell, Montana, 59901
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
Sands Cancer Center
Canandiaqua, New York, 14424
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Northern Westchester Hospital
Mount Kisco, New York, 10549
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Upstate Cancer Center Radiation Oncology at Oswego
Oswego, New York, 13126
Wilmot Cancer Institute Radiation Oncology at Greece
Rochester, New York, 14606
University of Rochester
Rochester, New York, 14642
State University of New York Upstate Medical University
Syracuse, New York, 13210
Upstate Cancer Center at Hill Radiation Oncology
Syracuse, New York, 13210
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
Upstate Cancer Center at Verona
Verona, New York, 13478
Wilmot Cancer Institute at Webster
Webster, New York, 14580
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Case Western Reserve University
Cleveland, Ohio, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Riverside Methodist Hospital
Columbus, Ohio, 43214
Grant Medical Center
Columbus, Ohio, 43215
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, 43015
Grady Memorial Hospital
Delaware, Ohio, 43015
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060
Mercy Health - Perrysburg Hospital
Perrysburg, Ohio, 43551
Mercy Health - Saint Anne Hospital
Toledo, Ohio, 43623
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Luke's Cancer Center - Allentown
Allentown, Pennsylvania, 18104
UPMC Altoona
Altoona, Pennsylvania, 16601
Saint Luke's University Hospital-Bethlehem Campus
Bethlehem, Pennsylvania, 18015
Carlisle Regional Cancer Center
Carlisle, Pennsylvania, 17015
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Chambersburg Hospital
Chambersburg, Pennsylvania, 17201
Geisinger Medical Center
Danville, Pennsylvania, 17822
Saint Luke's Hospital-Anderson Campus
Easton, Pennsylvania, 18045
Ephrata Cancer Center
Ephrata, Pennsylvania, 17522
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505
Saint Vincent Hospital
Erie, Pennsylvania, 16544
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania, 16121
Adams Cancer Center
Gettysburg, Pennsylvania, 17325
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109
Sechler Family Cancer Center
Lebanon, Pennsylvania, 17042
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837
UPMC Cancer Center - Monroeville
Monroeville, Pennsylvania, 15146
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Jefferson Torresdale Hospital
Philadelphia, Pennsylvania, 19114
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
Saint Luke's Hospital - Upper Bucks Campus
Quakertown, Pennsylvania, 18951
Saint Luke's Hospital-Quakertown Campus
Quakertown, Pennsylvania, 18951
Saint Luke's Hospital - Monroe Campus
Stroudsburg, Pennsylvania, 18360
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Divine Providence Hospital
Williamsport, Pennsylvania, 17754
WellSpan Health-York Cancer Center
York, Pennsylvania, 17403
WellSpan Health-York Hospital
York, Pennsylvania, 17403
UPMC Memorial
York, Pennsylvania, 17408
McLeod Regional Medical Center
Florence, South Carolina, 29506
Gibbs Cancer Center-Gaffney
Gaffney, South Carolina, 29341
Self Regional Healthcare
Greenwood, South Carolina, 29646
Gibbs Cancer Center-Pelham
Greer, South Carolina, 29651
Spartanburg Medical Center
Spartanburg, South Carolina, 29303
SMC Center for Hematology Oncology Union
Union, South Carolina, 29379
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
MD Anderson in The Woodlands
Conroe, Texas, 77384
M D Anderson Cancer Center
Houston, Texas, 77030
MD Anderson West Houston
Houston, Texas, 77079
MD Anderson League City
League City, Texas, 77573
MD Anderson in Sugar Land
Sugar Land, Texas, 77478
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154
Aspirus Cancer Care - James Beck Cancer Center
Rhinelander, Wisconsin, 54501
Aspirus Cancer Care - Stevens Point
Stevens Point, Wisconsin, 54481
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095