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

Who is this study for? Patients with Lung Cancer
Status: Recruiting
Location: See all (223) locations...
Intervention Type: Procedure, Other, Radiation, Drug
Study Type: Interventional
Study Phase: Phase 3
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

Locations
United States
Arizona
Mayo Clinic Hospital in Arizona
ACTIVE_NOT_RECRUITING
Phoenix
California
Kaiser Permanente-Anaheim
RECRUITING
Anaheim
Kaiser Permanente-Bellflower
RECRUITING
Bellflower
Kaiser Permanente Los Angeles Medical Center
RECRUITING
Los Angeles
Los Angeles General Medical Center
RECRUITING
Los Angeles
USC / Norris Comprehensive Cancer Center
RECRUITING
Los Angeles
Kaiser Permanente-Ontario
RECRUITING
Ontario
Colorado
UCHealth University of Colorado Hospital
ACTIVE_NOT_RECRUITING
Aurora
Memorial Hospital North
ACTIVE_NOT_RECRUITING
Colorado Springs
UCHealth Memorial Hospital Central
ACTIVE_NOT_RECRUITING
Colorado Springs
Connecticut
Smilow Cancer Hospital Care Center at Greenwich
TERMINATED
Greenwich
Smilow Cancer Hospital Care Center - Guilford
TERMINATED
Guilford
Smilow Cancer Center/Yale-New Haven Hospital
TERMINATED
New Haven
Yale University
TERMINATED
New Haven
Smilow Cancer Hospital Care Center-Trumbull
TERMINATED
Trumbull
Smilow Cancer Hospital Care Center - Waterford
TERMINATED
Waterford
Delaware
Beebe Medical Center
RECRUITING
Lewes
Christiana Care Health System-Christiana Hospital
RECRUITING
Newark
Delaware Clinical and Laboratory Physicians PA
SUSPENDED
Newark
Helen F Graham Cancer Center
RECRUITING
Newark
Medical Oncology Hematology Consultants PA
RECRUITING
Newark
Beebe Health Campus
RECRUITING
Rehoboth Beach
Christiana Care Health System-Wilmington Hospital
RECRUITING
Wilmington
Florida
UM Sylvester Comprehensive Cancer Center at Coral Gables
ACTIVE_NOT_RECRUITING
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
ACTIVE_NOT_RECRUITING
Deerfield Beach
University of Florida Health Science Center - Gainesville
ACTIVE_NOT_RECRUITING
Gainesville
University of Miami Miller School of Medicine-Sylvester Cancer Center
ACTIVE_NOT_RECRUITING
Miami
Moffitt Cancer Center
RECRUITING
Tampa
Moffitt Cancer Center - McKinley Campus
RECRUITING
Tampa
Moffitt Cancer Center-International Plaza
RECRUITING
Tampa
Moffitt Cancer Center at Wesley Chapel
RECRUITING
Wesley Chapel
Georgia
Emory Saint Joseph's Hospital
ACTIVE_NOT_RECRUITING
Atlanta
Emory University Hospital Midtown
ACTIVE_NOT_RECRUITING
Atlanta
Emory University Hospital/Winship Cancer Institute
ACTIVE_NOT_RECRUITING
Atlanta
Northside Hospital
RECRUITING
Atlanta
Northside Hospital-Cherokee
RECRUITING
Canton
Northside Hospital-Forsyth
RECRUITING
Cumming
Memorial Health University Medical Center
RECRUITING
Savannah
Iowa
Mary Greeley Medical Center
RECRUITING
Ames
McFarland Clinic - Ames
RECRUITING
Ames
Illinois
Rush-Copley Medical Center
RECRUITING
Aurora
Centralia Oncology Clinic
RECRUITING
Centralia
Rush University Medical Center
ACTIVE_NOT_RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
SUSPENDED
Chicago
Carle at The Riverfront
RECRUITING
Danville
Cancer Care Specialists of Illinois - Decatur
RECRUITING
Decatur
Decatur Memorial Hospital
RECRUITING
Decatur
Northwestern Medicine Cancer Center Kishwaukee
RECRUITING
Dekalb
Carle Physician Group-Effingham
RECRUITING
Effingham
Crossroads Cancer Center
RECRUITING
Effingham
Northwestern Medicine Cancer Center Delnor
RECRUITING
Geneva
Carle Physician Group-Mattoon/Charleston
RECRUITING
Mattoon
UC Comprehensive Cancer Center at Silver Cross
SUSPENDED
New Lenox
Cancer Care Center of O'Fallon
RECRUITING
O'fallon
HSHS Saint Elizabeth's Hospital
RECRUITING
O'fallon
OSF Saint Francis Medical Center
RECRUITING
Peoria
Carle Cancer Center
RECRUITING
Urbana
The Carle Foundation Hospital
RECRUITING
Urbana
Northwestern Medicine Cancer Center Warrenville
RECRUITING
Warrenville
Indiana
IU Health West Hospital
RECRUITING
Avon
IU Health North Hospital
RECRUITING
Carmel
Goshen Center for Cancer Care
RECRUITING
Goshen
Indiana University/Melvin and Bren Simon Cancer Center
RECRUITING
Indianapolis
IU Health Methodist Hospital
RECRUITING
Indianapolis
Kentucky
Baptist Health Lexington
ACTIVE_NOT_RECRUITING
Lexington
The James Graham Brown Cancer Center at University of Louisville
RECRUITING
Louisville
UofL Health Medical Center Northeast
RECRUITING
Louisville
Louisiana
Mary Bird Perkins Cancer Center
RECRUITING
Baton Rouge
Massachusetts
Boston Medical Center
RECRUITING
Boston
Maryland
Luminis Health Anne Arundel Medical Center
ACTIVE_NOT_RECRUITING
Annapolis
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
SUSPENDED
Baltimore
University of Maryland/Greenebaum Cancer Center
RECRUITING
Baltimore
UM Upper Chesapeake Medical Center
RECRUITING
Bel Air
Central Maryland Radiation Oncology in Howard County
RECRUITING
Columbia
University of Maryland Shore Medical Center at Easton
RECRUITING
Easton
UM Baltimore Washington Medical Center/Tate Cancer Center
RECRUITING
Glen Burnie
TidalHealth Richard A Henson Cancer Institute
ACTIVE_NOT_RECRUITING
Ocean Pines
TidalHealth Peninsula Regional
ACTIVE_NOT_RECRUITING
Salisbury
Michigan
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
RECRUITING
Ann Arbor
McLaren Cancer Institute-Bay City
RECRUITING
Bay City
Trinity Health IHA Medical Group Hematology Oncology - Brighton
RECRUITING
Brighton
Trinity Health Medical Center - Brighton
RECRUITING
Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton
RECRUITING
Canton
Trinity Health Medical Center - Canton
RECRUITING
Canton
Caro Cancer Center
SUSPENDED
Caro
Chelsea Hospital
RECRUITING
Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
RECRUITING
Chelsea
Wayne State University/Karmanos Cancer Institute
RECRUITING
Detroit
Weisberg Cancer Treatment Center
RECRUITING
Farmington Hills
McLaren Cancer Institute-Flint
RECRUITING
Flint
Karmanos Cancer Institute at McLaren Greater Lansing
RECRUITING
Lansing
McLaren Cancer Institute-Lapeer Region
RECRUITING
Lapeer
Trinity Health Saint Mary Mercy Livonia Hospital
RECRUITING
Livonia
Saint Mary's Oncology/Hematology Associates of Marlette
SUSPENDED
Marlette
McLaren Cancer Institute-Macomb
RECRUITING
Mount Clemens
McLaren Cancer Institute-Northern Michigan
RECRUITING
Petoskey
McLaren-Port Huron
RECRUITING
Port Huron
MyMichigan Medical Center Saginaw
RECRUITING
Saginaw
Oncology Hematology Associates of Saginaw Valley PC
SUSPENDED
Saginaw
MyMichigan Medical Center Tawas
RECRUITING
Tawas City
Saint Mary's Oncology/Hematology Associates of West Branch
SUSPENDED
West Branch
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
RECRUITING
Ypsilanti
Minnesota
Sanford Joe Lueken Cancer Center
RECRUITING
Bemidji
Minnesota Oncology - Burnsville
RECRUITING
Burnsville
Mercy Hospital
RECRUITING
Coon Rapids
Fairview Southdale Hospital
RECRUITING
Edina
Unity Hospital
ACTIVE_NOT_RECRUITING
Fridley
Fairview Clinics and Surgery Center Maple Grove
RECRUITING
Maple Grove
Minnesota Oncology Hematology PA-Maplewood
RECRUITING
Maplewood
Abbott-Northwestern Hospital
RECRUITING
Minneapolis
Monticello Cancer Center
RECRUITING
Monticello
Coborn Cancer Center at Saint Cloud Hospital
RECRUITING
Saint Cloud
Regions Hospital
RECRUITING
Saint Paul
United Hospital
RECRUITING
Saint Paul
Lakeview Hospital
RECRUITING
Stillwater
Minnesota Oncology Hematology PA-Woodbury
RECRUITING
Woodbury
Missouri
Saint Francis Medical Center
RECRUITING
Cape Girardeau
Parkland Health Center - Farmington
RECRUITING
Farmington
Freeman Health System
RECRUITING
Joplin
Sainte Genevieve County Memorial Hospital
RECRUITING
Sainte Genevieve
Mercy Hospital Springfield
RECRUITING
Springfield
Missouri Baptist Medical Center
RECRUITING
St Louis
Missouri Baptist Sullivan Hospital
RECRUITING
Sullivan
BJC Outpatient Center at Sunset Hills
RECRUITING
Sunset Hills
Montana
Billings Clinic Cancer Center
SUSPENDED
Billings
Benefis Sletten Cancer Institute
SUSPENDED
Great Falls
Logan Health Medical Center
SUSPENDED
Kalispell
North Carolina
Wake Forest University Health Sciences
RECRUITING
Winston-salem
North Dakota
Sanford Bismarck Medical Center
RECRUITING
Bismarck
Sanford Broadway Medical Center
RECRUITING
Fargo
Sanford Roger Maris Cancer Center
RECRUITING
Fargo
New Jersey
Cooper Hospital University Medical Center
RECRUITING
Camden
New York
Sands Cancer Center
ACTIVE_NOT_RECRUITING
Canandaigua
Northwell Health/Center for Advanced Medicine
ACTIVE_NOT_RECRUITING
Lake Success
Northern Westchester Hospital
ACTIVE_NOT_RECRUITING
Mount Kisco
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
ACTIVE_NOT_RECRUITING
New York
Upstate Cancer Center Radiation Oncology at Oswego
RECRUITING
Oswego
University of Rochester
ACTIVE_NOT_RECRUITING
Rochester
Wilmot Cancer Institute Radiation Oncology at Greece
ACTIVE_NOT_RECRUITING
Rochester
State University of New York Upstate Medical University
RECRUITING
Syracuse
Upstate Cancer Center at Hill Radiation Oncology
RECRUITING
Syracuse
Montefiore Medical Center - Moses Campus
ACTIVE_NOT_RECRUITING
The Bronx
Montefiore Medical Center-Einstein Campus
ACTIVE_NOT_RECRUITING
The Bronx
Montefiore Medical Center-Weiler Hospital
ACTIVE_NOT_RECRUITING
The Bronx
Upstate Cancer Center at Verona
SUSPENDED
Verona
Wilmot Cancer Institute at Webster
ACTIVE_NOT_RECRUITING
Webster
Ohio
University of Cincinnati Cancer Center-UC Medical Center
RECRUITING
Cincinnati
Case Western Reserve University
RECRUITING
Cleveland
Grant Medical Center
RECRUITING
Columbus
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Riverside Methodist Hospital
RECRUITING
Columbus
Delaware Health Center-Grady Cancer Center
RECRUITING
Delaware
Grady Memorial Hospital
RECRUITING
Delaware
UH Seidman Cancer Center at Lake Health Mentor Campus
RECRUITING
Mentor
Mercy Health - Perrysburg Hospital
RECRUITING
Perrysburg
Mercy Health - Saint Anne Hospital
SUSPENDED
Toledo
University of Cincinnati Cancer Center-West Chester
RECRUITING
West Chester
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Pennsylvania
Saint Luke's Cancer Center - Allentown
ACTIVE_NOT_RECRUITING
Allentown
UPMC Altoona
RECRUITING
Altoona
Saint Luke's University Hospital-Bethlehem Campus
ACTIVE_NOT_RECRUITING
Bethlehem
Carlisle Regional Cancer Center
RECRUITING
Carlisle
Christiana Care Health System-Concord Health Center
RECRUITING
Chadds Ford
Chambersburg Hospital
RECRUITING
Chambersburg
Geisinger Medical Center
RECRUITING
Danville
Saint Luke's Hospital-Anderson Campus
ACTIVE_NOT_RECRUITING
Easton
Ephrata Cancer Center
RECRUITING
Ephrata
Saint Vincent Hospital
ACTIVE_NOT_RECRUITING
Erie
Adams Cancer Center
RECRUITING
Gettysburg
UPMC Cancer Centers - Arnold Palmer Pavilion
RECRUITING
Greensburg
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
RECRUITING
Harrisburg
Sechler Family Cancer Center
RECRUITING
Lebanon
Geisinger Medical Oncology-Lewisburg
RECRUITING
Lewisburg
UPMC Cancer Center - Monroeville
RECRUITING
Monroeville
Jefferson Torresdale Hospital
SUSPENDED
Philadelphia
Thomas Jefferson University Hospital
SUSPENDED
Philadelphia
Allegheny General Hospital
ACTIVE_NOT_RECRUITING
Pittsburgh
UPMC-Magee Womens Hospital
RECRUITING
Pittsburgh
UPMC-Passavant Hospital
RECRUITING
Pittsburgh
UPMC-Presbyterian Hospital
RECRUITING
Pittsburgh
UPMC-Saint Clair Hospital Cancer Center
RECRUITING
Pittsburgh
UPMC-Saint Margaret
RECRUITING
Pittsburgh
UPMC-Shadyside Hospital
RECRUITING
Pittsburgh
Saint Luke's Hospital - Upper Bucks Campus
ACTIVE_NOT_RECRUITING
Quakertown
Saint Luke's Hospital-Quakertown Campus
SUSPENDED
Quakertown
Saint Luke's Hospital - Monroe Campus
ACTIVE_NOT_RECRUITING
Stroudsburg
Geisinger Wyoming Valley/Henry Cancer Center
RECRUITING
Wilkes-barre
Divine Providence Hospital
RECRUITING
Williamsport
UPMC Memorial
RECRUITING
York
WellSpan Health-York Cancer Center
RECRUITING
York
WellSpan Health-York Hospital
RECRUITING
York
South Carolina
McLeod Regional Medical Center
RECRUITING
Florence
Gibbs Cancer Center-Gaffney
ACTIVE_NOT_RECRUITING
Gaffney
Self Regional Healthcare
RECRUITING
Greenwood
Gibbs Cancer Center-Pelham
ACTIVE_NOT_RECRUITING
Greer
Spartanburg Medical Center
ACTIVE_NOT_RECRUITING
Spartanburg
SMC Center for Hematology Oncology Union
ACTIVE_NOT_RECRUITING
Union
South Dakota
Avera Cancer Institute
ACTIVE_NOT_RECRUITING
Sioux Falls
Sanford Cancer Center Oncology Clinic
RECRUITING
Sioux Falls
Sanford USD Medical Center - Sioux Falls
RECRUITING
Sioux Falls
Texas
MD Anderson in The Woodlands
RECRUITING
Conroe
M D Anderson Cancer Center
RECRUITING
Houston
MD Anderson West Houston
RECRUITING
Houston
MD Anderson League City
RECRUITING
League City
MD Anderson in Sugar Land
RECRUITING
Sugar Land
Virginia
VCU Massey Comprehensive Cancer Center
ACTIVE_NOT_RECRUITING
Richmond
Wisconsin
Langlade Hospital and Cancer Center
RECRUITING
Antigo
ThedaCare Regional Cancer Center
RECRUITING
Appleton
Gundersen Lutheran Medical Center
ACTIVE_NOT_RECRUITING
La Crosse
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
RECRUITING
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Froedtert Menomonee Falls Hospital
RECRUITING
Menomonee Falls
Medical College of Wisconsin
RECRUITING
Milwaukee
Cancer Center of Western Wisconsin
RECRUITING
New Richmond
Drexel Town Square Health Center
RECRUITING
Oak Creek
Aspirus Cancer Care - James Beck Cancer Center
RECRUITING
Rhinelander
Aspirus Cancer Care - Stevens Point
RECRUITING
Stevens Point
Aspirus Regional Cancer Center
RECRUITING
Wausau
Froedtert West Bend Hospital/Kraemer Cancer Center
RECRUITING
West Bend
Other Locations
Canada
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
RECRUITING
Québec
Allan Blair Cancer Centre
RECRUITING
Regina
Saskatoon Cancer Centre
RECRUITING
Saskatoon
University Health Network-Princess Margaret Hospital
SUSPENDED
Toronto
Time Frame
Start Date: 2021-06-10
Estimated Completion Date: 2030-07-01
Participants
Target number of participants: 200
Treatments
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.
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.
Sponsors
Leads: NRG Oncology
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov