Recruiting
Phase 3

HA-WBRT & Memantine

Sponsor:

Canadian Cancer Trials Group

Code:

NCT03550391

Conditions

Brain Metastases

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Memantine

Hippocampal-avoidant (HA-WBRT) Radiotherapy

Stereotactic Radiosurgery (SRS)

Study Details

Brief summary:

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.

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.

Conditions

Brain Metastases

Study ID

NCT03550391

Start date

Nov 22, 2018

Status verified date

Apr, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Pregnant or nursing women.
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.
  • Inability to complete a brain MRI.
  • Known allergy to gadolinium.
  • Prior cranial radiation therapy.
  • Planned cytotoxic chemotherapy within 48 hours prior or after the SRS or HA-WBRT.
  • 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.
  • Surgical resection of a brain metastasis (stereotactic biopsies will be allowed).
  • 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.
  • Prior allergic reaction to memantine.
  • Current alcohol or drug abuse.
  • Current use of NMDA antagonists, such as amantadine, ketamine, or dextromethorphan.
  • Diagnosis of chronic liver disease/cirrhosis of the liver (e.g. Child-Pugh class B or C).
  • Patients with architectural distortion of lateral ventricular systems, which, in the opinion of the local investigator, makes hippocampal delineation challenging

Study Design

Enrollment

206 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Hippocampal-avoidant (HA-WBRT) plus Memantine

WBRT 30Gy in 10 fractions + memantine

experimental: Stereotactic Radiosurgery (SRS)

SRS 18-20 or 22Gy in single fraction

Interventions

Memantine

20 mg (10 mg divided twice daily). Dose will be escalated by 5 mg per week. Memantine should start at 5 mg, and then increased in 5 mg increments at the following schedule, depending on the patient's response and tolerance:

Hippocampal-avoidant (HA-WBRT) Radiotherapy

30Gy in 10 fractions

Stereotactic Radiosurgery (SRS)

18-20 or 22 Gy in single fraction

Primary outcome measure

  • Overall Survival [ Time Frame: 4.5 years ]
  • Neurocognitive progression-free survival [ Time Frame: 4.5 years ]

Central Contacts and Locations

Central contacts

Chris O'Callaghan

613-533-6430cocallaghan@ctg.queensu.ca

Locations

University of Arizona Cancer Center-Orange Grove Campus

Recruiting

Tucson, Arizona, United States, 85704

Contacts

Site Public Contact

520-694-8900

Principal Investigator:

Baldassarre Stea

University of Arizona Cancer Center-North Campus

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Site Public Contact

UACC-IIT@uacc.arizona.edu

Principal Investigator:

Baldassarre Stea

City of Hope Corona

Recruiting

Corona, California, United States, 92882

Contacts

Site Public Contact

626-256-4673becomingapatient@coh.org

Principal Investigator:

Sean Szeja

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Sean Szeja

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Site Public Contact

877-467-3411

Principal Investigator:

Sean Szeja

City of Hope Antelope Valley

Recruiting

Lancaster, California, United States, 93534

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Sean Szeja

City of Hope South Pasadena

Recruiting

South Pasadena, California, United States, 91030

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Sean Szeja

City of Hope South Bay

Recruiting

Torrance, California, United States, 90503

Contacts

Site Public Contact

877-467-3411

Principal Investigator:

Sean Szeja

City of Hope Upland

Recruiting

Upland, California, United States, 91786

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Sean Szeja

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Benjamin J. Rich

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Benjamin J. Rich

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Benjamin J. Rich

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Benjamin J. Rich

Decatur Memorial Hospital

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

HSHS Saint Elizabeth's Hospital

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Methodist Medical Center of Illinois

Recruiting

Peoria, Illinois, United States, 61636

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

OSF Saint Francis Medical Center

Recruiting

Peoria, Illinois, United States, 61637

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Carle Cancer Center

Recruiting

Urbana, Illinois, United States, 61801

Contacts

Site Public Contact

800-446-5532Research@carle.com

Principal Investigator:

Daniel H. Barnett

Iowa Methodist Medical Center

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-6727

Principal Investigator:

Seema Harichand-Herdt

Walter Reed National Military Medical Center

Recruiting

Bethesda, Maryland, United States, 20889-5600

Contacts

Site Public Contact

301-319-2100

Principal Investigator:

Corbin A. Helis

Tufts Medical Center

Recruiting

Boston, Massachusetts, United States, 02111

Contacts

Site Public Contact

617-636-5000ContactUsCancerCenter@TuftsMedicalCenter.org

Principal Investigator:

John E. Mignano

University of Michigan Rogel Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Site Public Contact

800-865-1125CancerAnswerLine@med.umich.edu

Principal Investigator:

Michelle M. Kim

Saint Francis Medical Center

Recruiting

Cape Girardeau, Missouri, United States, 63703

Contacts

Site Public Contact

573-334-2230sfmc@sfmc.net

Principal Investigator:

Bryan A. Faller

Siteman Cancer Center at Saint Peters Hospital

Recruiting

City of Saint Peters, Missouri, United States, 63376

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Siteman Cancer Center at West County Hospital

Recruiting

Creve Coeur, Missouri, United States, 63141

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Siteman Cancer Center-South County

Recruiting

St Louis, Missouri, United States, 63129

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Missouri Baptist Medical Center

Recruiting

St Louis, Missouri, United States, 63131

Contacts

Site Public Contact

314-996-5569

Principal Investigator:

Bryan A. Faller

Benefis Sletten Cancer Institute

Recruiting

Great Falls, Montana, United States, 59405

Contacts

Site Public Contact

406-969-6060mccinfo@mtcancer.org

Principal Investigator:

John M. Schallenkamp

AtlantiCare Surgery Center

Recruiting

Egg Harbor, New Jersey, United States, 08234

Contacts

Site Public Contact

609-748-7200

Principal Investigator:

James C. Wurzer

State University of New York Upstate Medical University

Recruiting

Syracuse, New York, United States, 13210

Contacts

Site Public Contact

315-464-5476

Principal Investigator:

Michael D. Mix

Cone Health Cancer Center

Recruiting

Greensboro, North Carolina, United States, 27403

Contacts

Site Public Contact

336-832-0836stacey.phelps@conehealth.com

Principal Investigator:

Sarah E. Squire

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

336-713-6771

Principal Investigator:

Michael D. Chan

Sanford Bismarck Medical Center

Recruiting

Bismarck, North Dakota, United States, 58501

Contacts

Site Public Contact

701-323-5760OncologyClinicalTrialsFargo@sanfordhealth.org

Principal Investigator:

Daniel Almquist

Legacy Good Samaritan Hospital and Medical Center

Recruiting

Portland, Oregon, United States, 97210

Contacts

Site Public Contact

800-220-4937cancer@lhs.org

Principal Investigator:

Andrew Y. Kee

Geisinger Medical Center

Recruiting

Danville, Pennsylvania, United States, 17822

Contacts

Site Public Contact

570-271-5251HemonCCTrials@geisinger.edu

Principal Investigator:

Heath B. Mackley

Geisinger Wyoming Valley/Henry Cancer Center

Recruiting

Wilkes-Barre, Pennsylvania, United States, 18711

Contacts

Site Public Contact

570-271-5251HemonCCTrials@geisinger.edu

Principal Investigator:

Heath B. Mackley

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-805-3666

Principal Investigator:

Michael W. Straza

Arthur J E Child Comprehensive Cancer Centre

Recruiting

Calgary, Alberta, Canada, T2N 5G2

Contacts

Site Public Contact

888-823-5923ctsucontact@westat.com

Principal Investigator:

Muhammad S. Faruqi

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Contacts

Site Public Contact

780-432-8500

Principal Investigator:

Samir I. Patel

BCCA-Vancouver Cancer Centre

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Contacts

Site Public Contact

888-939-3333

Principal Investigator:

Alan M. Nichol

QEII Health Sciences Centre/Nova Scotia Health Authority

Recruiting

Halifax, Nova Scotia, Canada, B3H 2Y9

Contacts

Site Public Contact

902-473-6000

Principal Investigator:

Michael N. Ha

London Regional Cancer Program

Recruiting

London, Ontario, Canada, N6A 4L6

Contacts

Site Public Contact

519-685-8600

Principal Investigator:

Melody Qu

University Health Network-Princess Margaret Hospital

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Site Public Contact

416-946-4501clinical.trials@uhn.on.ca

Principal Investigator:

David B. Shultz

CHUM - Centre Hospitalier de l'Universite de Montreal

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Site Public Contact

514-890-8000info.cr.chum@ssss.gouv.qc.ca

Principal Investigator:

David Roberge

Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contacts

Site Public Contact

514-340-8222

Principal Investigator:

Thierry M. Muanza

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

Recruiting

Québec, Quebec, Canada, G1R 2J6

Contacts

Site Public Contact

rechclinique@crchuq.ulaval.ca

Principal Investigator:

Isabelle Thibault

More Information

Sponsor

Canadian Cancer Trials Group

Last update posted

Jun 9, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Canadian Cancer Trials Group on 2026-06-09.