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

NCT03550391 | Recruiting Phase 3 DMC FDA Device

• 2 other identifiers: CCTG CE.7NCI-2018-00395
• Study Type: interventional
• Target: 206
• Locations: 2 countries
• Sites: 86

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

Outcome Measures

Primary Outcomes (2)

• Overall Survival

  To compare the overall survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine

  4.5 years

• Neurocognitive progression-free survival

  To compare the neurocognitive progression-free survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine

  4.5 years

Secondary Outcomes (15)

• Time to central nervous system (CNS) failure (local, distant, and leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine

  4.5 years

• Difference in CNS failure patterns (local, distant, or leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine

  4.5 years

• Number of salvage procedures following SRS in comparison to HA-WBRT + memantine

  4.5 years

• Neurocognitive progression-free survival in patients who receive SRS compared to HA-WBRT + memantine

  4.5 years

• Tabulate and descriptively compare the post-treatment adverse events associated with the interventions.

  4.5 years

Study Arms (2)

Hippocampal-avoidant (HA-WBRT) plus Memantine

EXPERIMENTAL

WBRT 30Gy in 10 fractions + memantine

Drug: Memantine; Radiation: Hippocampal-avoidant (HA-WBRT) Radiotherapy

Stereotactic Radiosurgery (SRS)

EXPERIMENTAL

SRS 18-20 or 22Gy in single fraction

Procedure: Stereotactic Radiosurgery (SRS)

Interventions

Memantine 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) plus Memantine

Stereotactic Radiosurgery (SRS) PROCEDURE

18-20 or 22 Gy in single fraction

Stereotactic Radiosurgery (SRS)

Hippocampal-avoidant (HA-WBRT) Radiotherapy RADIATION

30Gy in 10 fractions

Hippocampal-avoidant (HA-WBRT) plus Memantine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Alliance for Clinical Trials in Oncology: collaborator
• NRG Oncology: collaborator

Study Sites (86)

University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, 85704, United States

RECRUITING

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

RECRUITING

City of Hope Corona

Corona, California, 92882, United States

RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

SUSPENDED

City of Hope Antelope Valley

Lancaster, California, 93534, United States

RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

ACTIVE NOT RECRUITING

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, 95670, United States

ACTIVE NOT RECRUITING

Rohnert Park Cancer Center

Rohnert Park, California, 94928, United States

ACTIVE NOT RECRUITING

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, 95678, United States

ACTIVE NOT RECRUITING

South Sacramento Cancer Center

Sacramento, California, 95823, United States

ACTIVE NOT RECRUITING

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051, United States

ACTIVE NOT RECRUITING

City of Hope South Pasadena

South Pasadena, California, 91030, United States

RECRUITING

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, 94080, United States

ACTIVE NOT RECRUITING

City of Hope South Bay

Torrance, California, 90503, United States

RECRUITING

City of Hope Upland

Upland, California, 91786, United States

RECRUITING

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

ACTIVE NOT RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

RECRUITING

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

ACTIVE NOT RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

ACTIVE NOT RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

ACTIVE NOT RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Piedmont Hospital

Atlanta, Georgia, 30309, United States

ACTIVE NOT RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

SUSPENDED

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

SUSPENDED

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

SUSPENDED

Northwestern University

Chicago, Illinois, 60611, United States

ACTIVE NOT RECRUITING

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

RECRUITING

Loyola University Medical Center

Maywood, Illinois, 60153, United States

SUSPENDED

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, 62269, United States

RECRUITING

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

RECRUITING

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

ACTIVE NOT RECRUITING

Community Cancer Center North

Indianapolis, Indiana, 46256, United States

ACTIVE NOT RECRUITING

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

RECRUITING

Luminis Health Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

ACTIVE NOT RECRUITING

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Regions Hospital

Saint Paul, Minnesota, 55101, United States

SUSPENDED

Saint Francis Medical Center

Cape Girardeau, Missouri, 63703, United States

RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

RECRUITING

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

RECRUITING

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

SUSPENDED

Benefis Sletten Cancer Institute

Great Falls, Montana, 59405, United States

RECRUITING

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

ACTIVE NOT RECRUITING

AtlantiCare Surgery Center

Egg Harbor, New Jersey, 08234, United States

RECRUITING

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

RECRUITING

SUNY Upstate Medical Center-Community Campus

Syracuse, New York, 13215, United States

SUSPENDED

Mission Hospital

Asheville, North Carolina, 28801, United States

ACTIVE NOT RECRUITING

Cone Health Cancer Center

Greensboro, North Carolina, 27403, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27834, United States

ACTIVE NOT RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

ACTIVE NOT RECRUITING

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

RECRUITING

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

RECRUITING

Fox Chase Cancer Center Buckingham

Furlong, Pennsylvania, 18925, United States

ACTIVE NOT RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

ACTIVE NOT RECRUITING

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, 18711, United States

RECRUITING

Self Regional Healthcare

Greenwood, South Carolina, 29646, United States

ACTIVE NOT RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

SUSPENDED

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont, 05819, United States

ACTIVE NOT RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

QEII Health Sciences Centre/Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

ACTIVE NOT RECRUITING

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

RECRUITING

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

CSSS Champlain-Charles Le Moyne

Greenfield Park, Quebec, J4V 2H1, Canada

SUSPENDED

CHUM - Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

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

Montreal, Quebec, H3H 2R9, Canada

SUSPENDED

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

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

Québec, Quebec, G1R 2J6, Canada

RECRUITING

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

SUSPENDED

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Memantine; Radiotherapy; Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• David Roberge

  CHUM-Centre Hospitalier de l'Universite de Montreal

  STUDY CHAIR

• Michael Chan

  Wake Forest School of Medicine, Winston-Salem, NC

  STUDY CHAIR

• Vina Gondi

  Northwestern Medicine Cancer Center, Warrenville IL

  STUDY CHAIR

Central Study Contacts

Chris O'Callaghan

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: June 8, 2018
• Study Start: November 22, 2018
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (13); US (73)