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

February 7, 2024 updated by: NRG Oncology

Phase III Trial of Stereotactic Radiosurgery (SRS) Versus Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for 10 or Fewer 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

Recruiting

Conditions

Intervention / Treatment

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 in patients receiving HA-WBRT plus memantine relative to SRS for brain metastases from SCLC has an effect on overall survival.

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.

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

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • 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
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Recruiting
        • Allan Blair Cancer Centre
        • Contact:
          • Site Public Contact
          • Phone Number: 306-766-2213
        • Principal Investigator:
          • Taskia Mir
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Recruiting
        • Saskatoon Cancer Centre
        • Principal Investigator:
          • Vijayananda Kundapur
        • Contact:
          • Site Public Contact
          • Phone Number: 306-655-2914
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital in Arizona
        • Principal Investigator:
          • Terence T. Sio
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC / Norris Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 323-865-0451
        • Principal Investigator:
          • Jason C. Ye
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Los Angeles General Medical Center
        • Principal Investigator:
          • Jason C. Ye
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • UCHealth University of Colorado Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 720-848-0650
        • Principal Investigator:
          • Timothy V. Waxweiler
      • Colorado Springs, Colorado, United States, 80909
        • Recruiting
        • UCHealth Memorial Hospital Central
        • Contact:
          • Site Public Contact
          • Phone Number: 719-365-2406
        • Principal Investigator:
          • Timothy V. Waxweiler
      • Colorado Springs, Colorado, United States, 80920
        • Recruiting
        • Memorial Hospital North
        • Contact:
          • Site Public Contact
          • Phone Number: 719-364-6700
        • Principal Investigator:
          • Timothy V. Waxweiler
    • Connecticut
      • Greenwich, Connecticut, United States, 06830
        • Recruiting
        • Smilow Cancer Hospital Care center at Greenwich
        • Principal Investigator:
          • Christin A. Knowlton
        • Contact:
      • Guilford, Connecticut, United States, 06437
        • Recruiting
        • Smilow Cancer Hospital Care Center - Guilford
        • Principal Investigator:
          • Christin A. Knowlton
        • Contact:
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Principal Investigator:
          • Christin A. Knowlton
        • Contact:
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Smilow Cancer Center/Yale-New Haven Hospital
        • Principal Investigator:
          • Christin A. Knowlton
        • Contact:
      • Trumbull, Connecticut, United States, 06611
        • Recruiting
        • Smilow Cancer Hospital Care Center-Trumbull
        • Principal Investigator:
          • Christin A. Knowlton
        • Contact:
      • Waterford, Connecticut, United States, 06385
        • Recruiting
        • Smilow Cancer Hospital Care Center - Waterford
        • Principal Investigator:
          • Christin A. Knowlton
        • Contact:
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Recruiting
        • Beebe Medical Center
        • Contact:
        • Principal Investigator:
          • Gregory A. Masters
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19713
        • Suspended
        • Delaware Clinical and Laboratory Physicians PA
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants PA
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19718
        • Recruiting
        • Christiana Care Health System-Christiana Hospital
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Rehoboth Beach, Delaware, United States, 19971
        • Recruiting
        • Beebe Health Campus
        • Contact:
        • Principal Investigator:
          • Gregory A. Masters
    • Florida
      • Coral Gables, Florida, United States, 33146
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Gregory A. Azzam
      • Deerfield Beach, Florida, United States, 33442
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Gregory A. Azzam
      • Gainesville, Florida, United States, 32610
        • Active, not recruiting
        • University of Florida Health Science Center - Gainesville
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Gregory A. Azzam
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
        • Principal Investigator:
          • Kristin A. Higgins
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Northside Hospital
        • Contact:
        • Principal Investigator:
          • Gena H. Volas-Redd
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory University Hospital Midtown
        • Contact:
          • Site Public Contact
          • Phone Number: 888-946-7447
        • Principal Investigator:
          • Kristin A. Higgins
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory Saint Joseph's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 404-851-7115
        • Principal Investigator:
          • Kristin A. Higgins
      • Canton, Georgia, United States, 30115
        • Recruiting
        • Northside Hospital-Cherokee
        • Contact:
        • Principal Investigator:
          • Gena H. Volas-Redd
      • Cumming, Georgia, United States, 30041
        • Recruiting
        • Northside Hospital-Forsyth
        • Contact:
        • Principal Investigator:
          • Gena H. Volas-Redd
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Recruiting
        • Rush - Copley Medical Center
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Centralia, Illinois, United States, 62801
        • Recruiting
        • Centralia Oncology Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Principal Investigator:
          • Gaurav Marwaha
        • Contact:
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Principal Investigator:
          • Steven J. Chmura
        • Contact:
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Peoria, Illinois, United States, 61637
        • Recruiting
        • OSF Saint Francis Medical Center
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • The Carle Foundation Hospital
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Recruiting
        • Goshen Center For Cancer Care
        • Contact:
        • Principal Investigator:
          • Irina Sparks
    • Iowa
      • Ames, Iowa, United States, 50010
        • Recruiting
        • Mary Greeley Medical Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Ames, Iowa, United States, 50010
        • Recruiting
        • McFarland Clinic - Ames
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Suspended
        • Baptist Health Lexington
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Recruiting
        • Mary Bird Perkins Cancer Center
        • Contact:
        • Principal Investigator:
          • Victor T. Lin
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Active, not recruiting
        • Anne Arundel Medical Center
      • Baltimore, Maryland, United States, 21237
        • Recruiting
        • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
        • Principal Investigator:
          • Kelly E. Orwat
        • Contact:
          • Site Public Contact
          • Phone Number: 443-777-7364
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Mark V. Mishra
      • Bel Air, Maryland, United States, 21014
        • Recruiting
        • UM Upper Chesapeake Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 443-643-3010
        • Principal Investigator:
          • Jack J. Hong
      • Columbia, Maryland, United States, 21044
        • Recruiting
        • Central Maryland Radiation Oncology in Howard County
        • Contact:
          • Site Public Contact
          • Phone Number: 443-546-1300
        • Principal Investigator:
          • Mark V. Mishra
      • Easton, Maryland, United States, 21601
        • Recruiting
        • University of Maryland Shore Medical Center at Easton
        • Principal Investigator:
          • John P. Mastandrea
        • Contact:
      • Ocean Pines, Maryland, United States, 21811
        • Recruiting
        • TidalHealth Richard A Henson Cancer Institute
        • Principal Investigator:
          • Zeinab Abou Yehia
        • Contact:
      • Salisbury, Maryland, United States, 21801
        • Recruiting
        • TidalHealth Peninsula Regional
        • Principal Investigator:
          • Zeinab Abou Yehia
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center
        • Principal Investigator:
          • Kimberley S. Mak
        • Contact:
          • Site Public Contact
          • Phone Number: 617-638-8265
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
      • Brighton, Michigan, United States, 48114
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Samir Narayan
      • Canton, Michigan, United States, 48188
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Samir Narayan
      • Caro, Michigan, United States, 48723
        • Suspended
        • Caro Cancer Center
      • Chelsea, Michigan, United States, 48118
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Samir Narayan
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Samir Narayan
      • Marlette, Michigan, United States, 48453
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of Marlette
      • Saginaw, Michigan, United States, 48601
        • Suspended
        • Ascension Saint Mary's Hospital
      • Saginaw, Michigan, United States, 48604
        • Suspended
        • Oncology Hematology Associates of Saginaw Valley PC
      • Tawas City, Michigan, United States, 48764
        • Suspended
        • Ascension Saint Joseph Hospital
      • West Branch, Michigan, United States, 48661
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Samir Narayan
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
      • Coon Rapids, Minnesota, United States, 55433
        • Recruiting
        • Mercy Hospital
        • Contact:
        • Principal Investigator:
          • Yan Ji
      • Edina, Minnesota, United States, 55435
        • Recruiting
        • Fairview Southdale Hospital
        • Contact:
        • Principal Investigator:
          • Yan Ji
      • Fridley, Minnesota, United States, 55432
        • Active, not recruiting
        • Unity Hospital
      • Maple Grove, Minnesota, United States, 55369
        • Recruiting
        • Fairview Clinics and Surgery Center Maple Grove
        • Contact:
        • Principal Investigator:
          • Yan Ji
      • Saint Paul, Minnesota, United States, 55101
        • Recruiting
        • Regions Hospital
        • Contact:
        • Principal Investigator:
          • Yan Ji
      • Stillwater, Minnesota, United States, 55082
        • Recruiting
        • Lakeview Hospital
        • Contact:
        • Principal Investigator:
          • Yan Ji
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
      • Farmington, Missouri, United States, 63640
        • Recruiting
        • Parkland Health Center - Farmington
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Joplin, Missouri, United States, 64804
        • Recruiting
        • Freeman Health System
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
      • Saint Louis, Missouri, United States, 63131
        • Recruiting
        • Missouri Baptist Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sainte Genevieve, Missouri, United States, 63670
        • Recruiting
        • Sainte Genevieve County Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Springfield, Missouri, United States, 65804
        • Recruiting
        • Mercy Hospital Springfield
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
          • Site Public Contact
          • Phone Number: 417-269-4520
      • Sullivan, Missouri, United States, 63080
        • Recruiting
        • Missouri Baptist Sullivan Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sunset Hills, Missouri, United States, 63127
        • Recruiting
        • BJC Outpatient Center at Sunset Hills
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
    • Montana
      • Great Falls, Montana, United States, 59405
        • Suspended
        • Benefis Healthcare- Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Recruiting
        • Kalispell Regional Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • New York
      • Bronx, New York, United States, 10461
        • Active, not recruiting
        • Montefiore Medical Center-Einstein Campus
      • Bronx, New York, United States, 10461
        • Active, not recruiting
        • Montefiore Medical Center-Weiler Hospital
      • Bronx, New York, United States, 10467
        • Active, not recruiting
        • Montefiore Medical Center - Moses Campus
      • Canandaigua, New York, United States, 14424
        • Recruiting
        • Sands Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 585-396-6161
        • Principal Investigator:
          • Yuhchyau Chen
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health/Center for Advanced Medicine
        • Principal Investigator:
          • Anuj Goenka
        • Contact:
          • Site Public Contact
          • Phone Number: 516-734-8896
      • Mount Kisco, New York, United States, 10549
        • Recruiting
        • Northern Westchester Hospital
        • Principal Investigator:
          • Anuj Goenka
        • Contact:
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Principal Investigator:
          • Yuhchyau Chen
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
      • Rochester, New York, United States, 14606
        • Recruiting
        • Wilmot Cancer Institute Radiation Oncology at Greece
        • Principal Investigator:
          • Yuhchyau Chen
        • Contact:
          • Site Public Contact
          • Phone Number: 585-758-7877
      • Syracuse, New York, United States, 13210
        • Recruiting
        • State University of New York Upstate Medical University
        • Contact:
          • Site Public Contact
          • Phone Number: 315-464-5476
        • Principal Investigator:
          • Michael D. Mix
      • Webster, New York, United States, 14580
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Principal Investigator:
          • Christina K. Cramer
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
      • Fargo, North Dakota, United States, 58122
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Cancer Center-UC Medical Center
        • Principal Investigator:
          • Kyle Wang
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Case Western Reserve University
        • Principal Investigator:
          • Prashant Vempati
        • Contact:
      • Columbus, Ohio, United States, 43214
        • Recruiting
        • Riverside Methodist Hospital
        • Principal Investigator:
          • Timothy D. Moore
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Principal Investigator:
          • Evan Thomas
        • Contact:
      • Mentor, Ohio, United States, 44060
        • Recruiting
        • UH Seidman Cancer Center at Lake Health Mentor Campus
        • Principal Investigator:
          • Prashant Vempati
        • Contact:
      • Perrysburg, Ohio, United States, 43551
        • Recruiting
        • Mercy Health Perrysburg Cancer Center
        • Principal Investigator:
          • Timothy D. Moore
        • Contact:
      • Toledo, Ohio, United States, 43623
        • Suspended
        • Mercy Health - Saint Anne Hospital
      • West Chester, Ohio, United States, 45069
        • Recruiting
        • University of Cincinnati Cancer Center-West Chester
        • Principal Investigator:
          • Kyle Wang
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Tyler Gunter
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18104
        • Recruiting
        • Saint Luke's Cancer Center - Allentown
        • Principal Investigator:
          • Nimisha Deb
        • Contact:
          • Site Public Contact
          • Phone Number: 610-776-4714
      • Bethlehem, Pennsylvania, United States, 18015
        • Recruiting
        • Saint Luke's University Hospital-Bethlehem Campus
        • Principal Investigator:
          • Nimisha Deb
        • Contact:
          • Site Public Contact
          • Phone Number: 484-503-4151
      • Chadds Ford, Pennsylvania, United States, 19317
        • Recruiting
        • Christiana Care Health System-Concord Health Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Chambersburg, Pennsylvania, United States, 17201
        • Recruiting
        • Chambersburg Hospital
        • Principal Investigator:
          • Amit B. Shah
        • Contact:
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Medical Center
        • Contact:
        • Principal Investigator:
          • Fiori Alite
      • Easton, Pennsylvania, United States, 18045
        • Recruiting
        • Saint Luke's Hospital-Anderson Campus
        • Principal Investigator:
          • Nimisha Deb
        • Contact:
      • Ephrata, Pennsylvania, United States, 17522
        • Recruiting
        • Ephrata Cancer Center
        • Principal Investigator:
          • Amit B. Shah
        • Contact:
          • Site Public Contact
          • Phone Number: 717-721-4840
      • Erie, Pennsylvania, United States, 16544
        • Recruiting
        • Saint Vincent Hospital
        • Principal Investigator:
          • Rodney E. Wegner
        • Contact:
          • Site Public Contact
          • Phone Number: 814-452-5000
      • Gettysburg, Pennsylvania, United States, 17325
        • Recruiting
        • Adams Cancer Center
        • Principal Investigator:
          • Amit B. Shah
        • Contact:
          • Site Public Contact
          • Phone Number: 877-441-7957
      • Lebanon, Pennsylvania, United States, 17042
        • Recruiting
        • Sechler Family Cancer Center
        • Principal Investigator:
          • Amit B. Shah
        • Contact:
      • Lewisburg, Pennsylvania, United States, 17837
        • Recruiting
        • Geisinger Medical Oncology-Lewisburg
        • Contact:
        • Principal Investigator:
          • Fiori Alite
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Principal Investigator:
          • Wenyin Shi
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19114
        • Recruiting
        • Jefferson Torresdale Hospital
        • Principal Investigator:
          • Wenyin Shi
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny General Hospital
        • Principal Investigator:
          • Rodney E. Wegner
        • Contact:
          • Site Public Contact
          • Phone Number: 877-284-2000
      • Quakertown, Pennsylvania, United States, 18951
        • Recruiting
        • Saint Luke's Hospital-Quakertown Campus
        • Principal Investigator:
          • Nimisha Deb
        • Contact:
          • Site Public Contact
          • Phone Number: 610-776-4714
      • Quakertown, Pennsylvania, United States, 18951
        • Recruiting
        • Saint Luke's Hospital - Upper Bucks Campus
        • Principal Investigator:
          • Nimisha Deb
        • Contact:
          • Site Public Contact
          • Phone Number: 610-776-4714
      • Stroudsburg, Pennsylvania, United States, 18360
        • Recruiting
        • Saint Luke's Hospital - Monroe Campus
        • Principal Investigator:
          • Nimisha Deb
        • Contact:
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Recruiting
        • Geisinger Wyoming Valley/Henry Cancer Center
        • Contact:
        • Principal Investigator:
          • Fiori Alite
      • York, Pennsylvania, United States, 17403
        • Recruiting
        • WellSpan Health-York Cancer Center
        • Principal Investigator:
          • Amit B. Shah
        • Contact:
          • Site Public Contact
          • Phone Number: 877-441-7957
      • York, Pennsylvania, United States, 17403
        • Recruiting
        • WellSpan Health-York Hospital
        • Principal Investigator:
          • Amit B. Shah
        • Contact:
          • Site Public Contact
          • Phone Number: 877-441-7957
    • South Carolina
      • Florence, South Carolina, United States, 29506
        • Recruiting
        • McLeod Regional Medical Center
        • Contact:
        • Principal Investigator:
          • Rajesh Bajaj
      • Gaffney, South Carolina, United States, 29341
        • Active, not recruiting
        • Gibbs Cancer Center-Gaffney
      • Greenwood, South Carolina, United States, 29646
        • Recruiting
        • Self Regional Healthcare
        • Contact:
        • Principal Investigator:
          • Charlotte Rivers
      • Greer, South Carolina, United States, 29651
        • Active, not recruiting
        • Gibbs Cancer Center-Pelham
      • Spartanburg, South Carolina, United States, 29303
        • Active, not recruiting
        • Spartanburg Medical Center
      • Union, South Carolina, United States, 29379
        • Active, not recruiting
        • MGC Hematology Oncology-Union
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
      • Sioux Falls, South Dakota, United States, 57117-5134
      • Sioux Falls, South Dakota, United States, 57105
        • Active, not recruiting
        • Avera Cancer Institute
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Active, not recruiting
        • Virginia Commonwealth University/Massey Cancer Center
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Recruiting
        • Langlade Hospital and Cancer Center
        • Contact:
        • Principal Investigator:
          • Andrew J. Huang
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Gundersen Lutheran Medical Center
        • Contact:
        • Principal Investigator:
          • Collin D. Driscoll
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-622-8922
        • Principal Investigator:
          • Andrew M. Baschnagel
      • Menomonee Falls, Wisconsin, United States, 53051
        • Recruiting
        • Froedtert Menomonee Falls Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 262-257-5100
        • Principal Investigator:
          • Lindsay L. Puckett
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-3666
        • Principal Investigator:
          • Lindsay L. Puckett
      • New Richmond, Wisconsin, United States, 54017
        • Recruiting
        • Cancer Center of Western Wisconsin
        • Contact:
        • Principal Investigator:
          • Yan Ji
      • Oak Creek, Wisconsin, United States, 53154
        • Recruiting
        • Drexel Town Square Health Center
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
        • Principal Investigator:
          • Lindsay L. Puckett
      • Rhinelander, Wisconsin, United States, 54501
        • Recruiting
        • Ascension Saint Mary's Hospital
        • Principal Investigator:
          • Andrew J. Huang
        • Contact:
      • Stevens Point, Wisconsin, United States, 54481
        • Recruiting
        • Ascension Saint Michael's Hospital
        • Principal Investigator:
          • Andrew J. Huang
        • Contact:
      • Wausau, Wisconsin, United States, 54401
        • Recruiting
        • Aspirus Regional Cancer Center
        • Principal Investigator:
          • Andrew J. Huang
        • Contact:
          • Site Public Contact
          • Phone Number: 877-405-6866
      • West Bend, Wisconsin, United States, 53095
        • Recruiting
        • Froedtert West Bend Hospital/Kraemer Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
        • Principal Investigator:
          • Lindsay L. Puckett

Participation Criteria

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

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

  • Ten or fewer brain metastases ≤ 3 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.

    • 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.
    • 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 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.
  • 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. Patients must have completed prior intracranial surgical resection at least 14 days prior to registration.
  • 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.

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.
  • Prior allergic reaction to memantine.
  • Intractable seizures while on adequate anticonvulsant therapy; more than 1 seizure per month for the past 2 months.
  • 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).

  • Severe, active co-morbidity defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

Study Plan

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

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (SRS)
Patients undergo SRS over 1 day (in some cases several days).
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
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.
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

Outcome Measure
Measure Description
Time Frame
Time to Neurocognitive Failure
Time Frame: 1 year
Neurocognitive failure is the first failure, defined as neurocognitive decline (decline vs. no decline) using the reliable change index (RCI) on at least one of the following tests: Hopkins Verbal Learning Test - Revised (HVLT-R), Controlled Oral Word Association (COWA) test, or Trail Making Test (TMT) Parts A and B.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preservation of Neurocognitive Function
Time Frame: 1 year
A mixed effects model will be used to assess changes of standardized neurocognitive scores across time using all available data while adjusting for stratification variables and other baseline characteristics. For discrete time point analyses, the change from baseline to each follow-up time point, will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
1 year
Perceived Difficulties in Cognition
Time Frame: 1 year
Measured by Patient Reported Outcomes Measurement Information System (PROMIS). For discrete time point analyses, the change from baseline to each follow-up time point, will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
1 year
Symptom Burden
Time Frame: 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. Mixed effects models will be used to assess changes of the four subscale scores (symptom severity, symptom interference, neurologic factor, and cognitive factor score) across time using all available data while adjusting for stratification variables and other baseline characteristics. For discrete time point analyses, the change from baseline to each follow-up time point, will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
1 year
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
Will be estimated using the Kaplan-Meier method (Kaplan 1958), and differences between treatment arms will be tested using the log rank test (Mantel 1966). The Cox proportional hazard model (Cox 1972) will be performed with the stratification variables and other baseline characteristics as fixed variables to assess the treatment effect while adjusting for patient specific risk factors such as number of brain metastases and its interaction with treatment, KPS, and time to salvage chemotherapy as a time varying covariate. A two-sided significance level of 0.05 will be used.
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
Gray's test will be used to assess between treatment arm comparisons (Gray 1988). Cause-specific Cox proportional hazards models will be used to evaluate the effect of stratification variables (DS-GPA and prior NCF testing exposure) and other baseline characteristics, such as KPS, and number of brain metastases and its interaction with treatment arm. A two-sided significance level of 0.05 will be used.
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: 10 years
Will be collected and descriptively compared between arms using Chi-square tests.
10 years
Incidence of adverse events
Time Frame: 10 years
Graded by Common Terminology Criteria for Adverse Events version 5.0. Counts of all adverse events (AEs) by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of grade 3+ AEs related to treatment and the rate of grade 3+ AEs regardless of relationship to treatment will be compared between treatment arms using a Chi-square test at a two-sided significance level of 0.05.
10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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: 10 years
10 years
Time to incidence of distant brain relapses
Time Frame: 10 years
10 years
Time to leptomeningeal dissemination
Time Frame: 10 years
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
Gray's test will be used to compare treatment arms (Gray 1988).
Baseline to first salvage treatment, assessed up to 10 years

Collaborators and Investigators

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

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • 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)

March 24, 2021

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2030

Study Registration Dates

First Submitted

March 9, 2021

First Submitted That Met QC Criteria

March 17, 2021

First Posted (Actual)

March 18, 2021

Study Record Updates

Last Update Posted (Actual)

February 9, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-CC009 (Other Identifier: CTEP)
  • UG1CA189867 (U.S. NIH Grant/Contract)
  • NCI-2020-11651 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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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