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

NCT ID: NCT03550391

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

206 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-22

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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The purpose of this research study is to compare the effects (good or bad) of receiving stereotactic radiosurgery (SRS) versus receiving hippocampal-avoidant whole brain radiotherapy (HA-WBRT) plus a drug called memantine, on brain metastases. Receiving SRS could control cancer that has spread to the brain.

This study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To decide if it is better, the study doctors will be looking to see if the stereotactic radiosurgery (SRS) helps to either slow the growth of cancer or stop it from coming back, compared to the usual approach. Doctors will also look to see if this new approach increases the life span of patients with this type of cancer, and if it helps with quality of life and cancer related symptoms.

The usual approach for patients who are not in a study is treatment with whole brain radiation therapy alone (WBRT).

Conditions

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Brain Metastases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is an international multi-centre, open-label, randomized phase III trial comparing stereotactic radiosurgery compared with hippocampal-avoidant whole brain radiotherapy (HA-WBRT) plus memantine for 5-15 brain metastases
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hippocampal-avoidant (HA-WBRT) plus Memantine

WBRT 30Gy in 10 fractions + memantine

Group Type EXPERIMENTAL

Memantine

Intervention Type DRUG

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

Intervention Type RADIATION

30Gy in 10 fractions

Stereotactic Radiosurgery (SRS)

SRS 18-20 or 22Gy in single fraction

Group Type EXPERIMENTAL

Stereotactic Radiosurgery (SRS)

Intervention Type PROCEDURE

18-20 or 22 Gy in single fraction

Interventions

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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:

Intervention Type DRUG

Hippocampal-avoidant (HA-WBRT) Radiotherapy

30Gy in 10 fractions

Intervention Type RADIATION

Stereotactic Radiosurgery (SRS)

18-20 or 22 Gy in single fraction

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Roberge

Role: STUDY_CHAIR

CHUM-Centre Hospitalier de l'Universite de Montreal

Michael Chan

Role: STUDY_CHAIR

Wake Forest School of Medicine, Winston-Salem, NC

Vina Gondi

Role: STUDY_CHAIR

Northwestern Medicine Cancer Center, Warrenville IL

Locations

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University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, United States

Site Status RECRUITING

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Site Status RECRUITING

City of Hope Corona

Corona, California, United States

Site Status RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status RECRUITING

City of Hope at Irvine Lennar

Irvine, California, United States

Site Status RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status SUSPENDED

City of Hope Antelope Valley

Lancaster, California, United States

Site Status RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status ACTIVE_NOT_RECRUITING

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States

Site Status ACTIVE_NOT_RECRUITING

Rohnert Park Cancer Center

Rohnert Park, California, United States

Site Status ACTIVE_NOT_RECRUITING

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States

Site Status ACTIVE_NOT_RECRUITING

South Sacramento Cancer Center

Sacramento, California, United States

Site Status ACTIVE_NOT_RECRUITING

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Site Status ACTIVE_NOT_RECRUITING

City of Hope South Pasadena

South Pasadena, California, United States

Site Status RECRUITING

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States

Site Status ACTIVE_NOT_RECRUITING

City of Hope South Bay

Torrance, California, United States

Site Status RECRUITING

City of Hope Upland

Upland, California, United States

Site Status RECRUITING

Boca Raton Regional Hospital

Boca Raton, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status RECRUITING

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status RECRUITING

Memorial Hospital West

Pembroke Pines, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Piedmont Hospital

Atlanta, Georgia, United States

Site Status ACTIVE_NOT_RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status SUSPENDED

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Site Status SUSPENDED

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Site Status SUSPENDED

Northwestern University

Chicago, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status RECRUITING

Loyola University Medical Center

Maywood, Illinois, United States

Site Status SUSPENDED

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, United States

Site Status RECRUITING

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status RECRUITING

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status RECRUITING

Carle Cancer Center

Urbana, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

Community Cancer Center North

Indianapolis, Indiana, United States

Site Status ACTIVE_NOT_RECRUITING

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Site Status RECRUITING

Luminis Health Anne Arundel Medical Center

Annapolis, Maryland, United States

Site Status ACTIVE_NOT_RECRUITING

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Tufts Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status ACTIVE_NOT_RECRUITING

Regions Hospital

Saint Paul, Minnesota, United States

Site Status RECRUITING

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status RECRUITING

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status RECRUITING

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status SUSPENDED

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status RECRUITING

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Site Status ACTIVE_NOT_RECRUITING

AtlantiCare Surgery Center

Egg Harbor, New Jersey, United States

Site Status RECRUITING

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status RECRUITING

SUNY Upstate Medical Center-Community Campus

Syracuse, New York, United States

Site Status SUSPENDED

Mission Hospital

Asheville, North Carolina, United States

Site Status ACTIVE_NOT_RECRUITING

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status RECRUITING

East Carolina University

Greenville, North Carolina, United States

Site Status ACTIVE_NOT_RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States

Site Status RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status ACTIVE_NOT_RECRUITING

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

Site Status RECRUITING

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status RECRUITING

Fox Chase Cancer Center Buckingham

Furlong, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, United States

Site Status RECRUITING

Self Regional Healthcare

Greenwood, South Carolina, United States

Site Status ACTIVE_NOT_RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status SUSPENDED

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont, United States

Site Status ACTIVE_NOT_RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, Canada

Site Status RECRUITING

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status RECRUITING

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Site Status RECRUITING

QEII Health Sciences Centre/Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Site Status RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status RECRUITING

London Regional Cancer Program

London, Ontario, Canada

Site Status SUSPENDED

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

CSSS Champlain-Charles Le Moyne

Greenfield Park, Quebec, Canada

Site Status SUSPENDED

CHUM - Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Site Status RECRUITING

The Research Institute of the McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Site Status SUSPENDED

Jewish General Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

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

Québec, Quebec, Canada

Site Status RECRUITING

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, Canada

Site Status SUSPENDED

Countries

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United States Canada

Central Contacts

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Chris O'Callaghan

Role: CONTACT

Phone: 613-533-6430

Email: [email protected]

Facility Contacts

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Site Public Contact

Role: primary

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Other Identifiers

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NCI-2018-00395

Identifier Type: OTHER

Identifier Source: secondary_id

CCTG CE.7

Identifier Type: -

Identifier Source: org_study_id