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Taking people in United StatesPhase 3

Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5 or More Brain Metastases

Key facts

Who runs it
Canadian Cancer Trials Group
Where
Ann Arbor, Annapolis, Asheville, Atlanta, Bethesda, Billings, Bismarck, Boca Raton, Boise, Boston, Cape Girardeau, Chicago, City of Saint Peters, Coral Gables, Corona, Creve Coeur, Danville, Decatur, Deerfield Beach, Des Moines, Duarte, Egg Harbor, Furlong, Great Falls, Greensboro, Greenville, Greenwood, Hollywood, Indianapolis, Irvine, Jacksonville, La Jolla, Lancaster, Lebanon, Maywood, Miami, Milwaukee, O'Fallon, Oklahoma City, Orange, Pembroke Pines, Peoria, Philadelphia, Plantation, Portland, Rancho Cordova, Rochester, Rohnert Park, Roseville, Sacramento, Saint Johnsbury, Saint Paul, Salt Lake City, Santa Clara, South Pasadena, South San Francisco, St Louis, Syracuse, Tampa, Torrance, Tucson, Upland, Urbana, Warrenville, Wilkes-Barre, and Winston-Salem, United StatesSee the 73 sitesAlso in 1 other country, 13 sites
Trial code
Status
Recruiting
Phase
Phase 3
People taking part
206 people, planned
Started
22 Nov 2018
Expected to end
31 Dec 2027
Type of study
Interventional, 2 groups
Treatments tested
  • Memantine
  • Hippocampal-avoidant (HA-WBRT) Radiotherapy
  • Stereotactic Radiosurgery (SRS)
Record updated
9 June 2026

Who can take part

Age
18 years and older
Sex
Women and men
Healthy volunteers
Cannot take part

The registry criteria, word for word

Show all 31 criteriaShow less

Who can take part

  • Patients must have 5 or more brain metastases as counted on a T1 contrast enhanced MRI obtained ≤ 30 days from randomization (maximum 15 brain metastases)
  • Patients must have a pathological diagnosis (cytological or histological) of a non-hematopoietic malignancy
  • The largest brain metastasis must measure <2.5 cm in maximal diameter
  • Centre must have the ability to treat patients with either a Gamma Knife, Cyberknife, or a linear accelerator-based radiosurgery system
  • Patient must be > 18 years of age
  • Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French either alone or with assistance
  • ECOG performance status 0, 1, or 2
  • Creatinine clearance must be ≥ 30 ml/min within 28 days prior to registration
  • The Neurocognitive Testing examiner must have credentialing confirming completion of the neurocognitive testing training
  • Facility is credentialed by IROC to perform SRS and HA-WBRT. The treating centre must have completed stereotactic radiosurgery credentialing of the specific system(s) to be used in study patients. The treating centre must have completed IMRT credintialing of this specific IMRT systems to be used in study patients for the purposes of HA-WBRT
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate
  • A similar process must be followed for sites outside of Canada as per their respective cooperative group's procedures
  • Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
  • In accordance with CCTG policy, protocol treatment is to begin within 14 days of patient enrolment
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method

Who cannot take part

  • Prior cranial radiation therapy
  • Planned cytotoxic chemotherapy within 48 hours prior or after the SRS or HA-WBRT
  • Surgical resection of a brain metastasis (stereotactic biopsies will be allowed)
  • Prior allergic reaction to memantine
  • Current alcohol or drug abuse
  • Known allergy to gadolinium
  • Diagnosis of chronic liver disease/cirrhosis of the liver (e.g. Child-Pugh class B or C)
  • Pregnant or nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Inability to complete a brain MRI
  • Primary germ cell tumour, small cell carcinoma, or lymphoma
  • Widespread definitive leptomeningeal metastasis. This includes cranial nerve palsy, leptomeningeal carcinomatosis, ependymal involvement, cranial nerve involvement on imaging, suspicious linear meningeal enhancement, or cerebrospinal fluid (CSF) positive for tumour cells
  • A brain metastasis that is located ≤ 5 mm of the optic chiasm or either optic nerve
  • More than 15 brain metastases on a volumetric T1 contrast MRI (voxels of 1mm or smaller) performed within the past 14 days, or more than 10 metastases in the case of a non-volumetric MRI
  • Current use of NMDA antagonists, such as amantadine, ketamine, or dextromethorphan
  • Patients with architectural distortion of lateral ventricular systems, which, in the opinion of the local investigator, makes hippocampal delineation challenging

Where in United States

Also in 1 other country, 13 sites

  • University of Michigan Rogel Cancer CenterAnn Arbor, United StatesContact: Michelle M. Kim (principal investigator)Taking people
  • Luminis Health Anne Arundel Medical CenterAnnapolis, United StatesNo longer taking part
  • Mission HospitalAsheville, United StatesNo longer taking part
  • Emory Saint Joseph's HospitalAtlanta, United StatesNo longer taking part
  • Emory University Hospital/Winship Cancer InstituteAtlanta, United StatesNo longer taking part
  • Piedmont HospitalAtlanta, United StatesNo longer taking part
  • Walter Reed National Military Medical CenterBethesda, United StatesContact: Corbin A. Helis (principal investigator)Taking people
  • Billings Clinic Cancer CenterBillings, United StatesNo longer taking part
  • Sanford Bismarck Medical CenterBismarck, United StatesContact: Daniel Almquist (principal investigator)Taking people
  • Boca Raton Regional HospitalBoca Raton, United StatesNo longer taking part
  • Saint Alphonsus Cancer Care Center-BoiseBoise, United StatesNo longer taking part
  • Tufts Medical CenterBoston, United StatesContact: John E. Mignano (principal investigator)Taking people
  • Saint Francis Medical CenterCape Girardeau, United StatesContact: Bryan A. Faller (principal investigator)Taking people
  • Northwestern UniversityChicago, United StatesNo longer taking part
  • Siteman Cancer Center at Saint Peters HospitalCity of Saint Peters, United StatesContact: Jiayi Huang (principal investigator)Taking people
  • UM Sylvester Comprehensive Cancer Center at Coral GablesCoral Gables, United StatesContact: Benjamin J. Rich (principal investigator)Taking people
  • City of Hope CoronaCorona, United StatesContact: Sean Szeja (principal investigator)Taking people
  • Siteman Cancer Center at West County HospitalCreve Coeur, United StatesContact: Jiayi Huang (principal investigator)Taking people
  • Geisinger Medical CenterDanville, United StatesContact: Heath B. Mackley (principal investigator)Taking people
  • Decatur Memorial HospitalDecatur, United StatesContact: Bryan A. Faller (principal investigator)Taking people
  • UM Sylvester Comprehensive Cancer Center at Deerfield BeachDeerfield Beach, United StatesContact: Benjamin J. Rich (principal investigator)Taking people
  • Iowa Methodist Medical CenterDes Moines, United StatesContact: Seema Harichand-Herdt (principal investigator)Taking people
  • City of Hope Comprehensive Cancer CenterDuarte, United StatesContact: Sean Szeja (principal investigator)Taking people
  • AtlantiCare Surgery CenterEgg Harbor, United StatesContact: James C. Wurzer (principal investigator)Taking people
  • Fox Chase Cancer Center BuckinghamFurlong, United StatesNo longer taking part
  • Benefis Sletten Cancer InstituteGreat Falls, United StatesContact: John M. Schallenkamp (principal investigator)Taking people
  • Cone Health Cancer CenterGreensboro, United StatesContact: Sarah E. Squire (principal investigator)Taking people
  • East Carolina UniversityGreenville, United StatesNo longer taking part
  • Self Regional HealthcareGreenwood, United StatesNo longer taking part
  • Memorial Regional Hospital/Joe DiMaggio Children's HospitalHollywood, United StatesNo longer taking part
  • Community Cancer Center NorthIndianapolis, United StatesNo longer taking part
  • City of Hope at Irvine LennarIrvine, United StatesContact: Sean Szeja (principal investigator)Taking people
  • Mayo Clinic in FloridaJacksonville, United StatesNo longer taking part
  • UC San Diego Moores Cancer CenterLa Jolla, United StatesNo longer taking part
  • City of Hope Antelope ValleyLancaster, United StatesContact: Sean Szeja (principal investigator)Taking people
  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterLebanon, United StatesNo longer taking part
  • Loyola University Medical CenterMaywood, United StatesNo longer taking part
  • University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, United StatesContact: Benjamin J. Rich (principal investigator)Taking people
  • Medical College of WisconsinMilwaukee, United StatesContact: Michael W. Straza (principal investigator)Taking people
  • HSHS Saint Elizabeth's HospitalO'Fallon, United StatesContact: Bryan A. Faller (principal investigator)Taking people
  • University of Oklahoma Health Sciences CenterOklahoma City, United StatesNo longer taking part
  • UC Irvine Health- Chao Family Comprehensive Cancer CenterOrange, United StatesNo longer taking part
  • Memorial Hospital WestPembroke Pines, United StatesNo longer taking part
  • Methodist Medical Center of IllinoisPeoria, United StatesContact: Bryan A. Faller (principal investigator)Taking people
  • OSF Saint Francis Medical CenterPeoria, United StatesContact: Bryan A. Faller (principal investigator)Taking people
  • Fox Chase Cancer CenterPhiladelphia, United StatesNo longer taking part
  • UM Sylvester Comprehensive Cancer Center at PlantationPlantation, United StatesContact: Benjamin J. Rich (principal investigator)Taking people
  • Legacy Good Samaritan Hospital and Medical CenterPortland, United StatesContact: Andrew Y. Kee (principal investigator)Taking people
  • Kaiser Permanente-Rancho Cordova Cancer CenterRancho Cordova, United StatesNo longer taking part
  • Mayo Clinic in RochesterRochester, United StatesNo longer taking part
  • Rohnert Park Cancer CenterRohnert Park, United StatesNo longer taking part
  • The Permanente Medical Group-Roseville Radiation OncologyRoseville, United StatesNo longer taking part
  • South Sacramento Cancer CenterSacramento, United StatesNo longer taking part
  • Dartmouth Cancer Center - NorthSaint Johnsbury, United StatesNo longer taking part
  • Regions HospitalSaint Paul, United StatesNo longer taking part
  • Huntsman Cancer Institute/University of UtahSalt Lake City, United StatesNo longer taking part
  • Kaiser Permanente Medical Center - Santa ClaraSanta Clara, United StatesNo longer taking part
  • City of Hope South PasadenaSouth Pasadena, United StatesContact: Sean Szeja (principal investigator)Taking people
  • Kaiser Permanente Cancer Treatment CenterSouth San Francisco, United StatesNo longer taking part
  • Missouri Baptist Medical CenterSt Louis, United StatesContact: Bryan A. Faller (principal investigator)Taking people
  • Siteman Cancer Center-South CountySt Louis, United StatesContact: Jiayi Huang (principal investigator)Taking people
  • Washington University School of MedicineSt Louis, United StatesContact: Jiayi Huang (principal investigator)Taking people
  • State University of New York Upstate Medical UniversitySyracuse, United StatesContact: Michael D. Mix (principal investigator)Taking people
  • SUNY Upstate Medical Center-Community CampusSyracuse, United StatesNo longer taking part
  • Moffitt Cancer CenterTampa, United StatesNo longer taking part
  • City of Hope South BayTorrance, United StatesContact: Sean Szeja (principal investigator)Taking people
  • University of Arizona Cancer Center-North CampusTucson, United StatesContact: Baldassarre Stea (principal investigator)Taking people
  • University of Arizona Cancer Center-Orange Grove CampusTucson, United StatesContact: Baldassarre Stea (principal investigator)Taking people
  • City of Hope UplandUpland, United StatesContact: Sean Szeja (principal investigator)Taking people
  • Carle Cancer CenterUrbana, United StatesContact: Daniel H. Barnett (principal investigator)Taking people
  • Northwestern Medicine Cancer Center WarrenvilleWarrenville, United StatesNo longer taking part
  • Geisinger Wyoming Valley/Henry Cancer CenterWilkes-Barre, United StatesContact: Heath B. Mackley (principal investigator)Taking people
  • Wake Forest University Health SciencesWinston-Salem, United StatesContact: Michael D. Chan (principal investigator)Taking people

About the trial

What the trial wants to find out

Stereotactic radiosurgery (SRS) is a commonly used treatment for brain tumors. It is a one-day (or in some cases two day), out-patient procedure during which a high dose of radiation is delivered to small spots in the brain while excluding the surrounding normal brain.

Read full original descriptionShow less

Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) is when radiation therapy is given to the whole brain, while trying to decrease the amount of radiation that is delivered to the area of the hippocampus. The hippocampus is a brain structure that is important for memory. Memantine is a drug that is given to help relieve symptoms that can be caused by WBRT, including problems with memory and other mental symptoms.

Health Canada, the regulatory body that oversees the use of drugs in Canada, has not approved the sale or use of memantine in combination with WBRT to treat this kind of cancer, although they have allowed its use in this study.

The 2 groups in the trial

  • Hippocampal-avoidant (HA-WBRT) plus MemantineTreatment being tested

    WBRT 30Gy in 10 fractions + memantine

    Treatment: Memantine and Hippocampal-avoidant (HA-WBRT) Radiotherapy

  • Stereotactic Radiosurgery (SRS)Treatment being tested

    SRS 18-20 or 22Gy in single fraction

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
Official title
A Phase III Trial of Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5 or More Brain Metastases
Record updated
9 June 2026
Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5 or More Brain Metastases (NCT03550391) – Frontlight Research