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Comparing two radiation treatments for brain metastases

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

Phase 3 Interventional Canadian Cancer Trials Group · NCT03550391

This study is testing whether a new type of targeted radiation treatment works better than a standard whole brain radiation treatment for people with multiple brain tumors.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment206 (estimated)
Ages18 Years and up
SexAll
SponsorCanadian Cancer Trials Group Research network
Drugs / interventionschemotherapy, radiation
Locations86 sites (Tucson, Arizona and 85 other locations)
Trial IDNCT03550391 on ClinicalTrials.gov

What this trial studies

This research compares the effectiveness of stereotactic radiosurgery (SRS) against hippocampal-avoidant whole brain radiotherapy (HA-WBRT) combined with memantine for patients with five or more brain metastases. The study aims to determine which treatment better controls cancer growth, improves survival rates, and enhances quality of life. Participants will be monitored for cancer progression and cognitive effects, with the goal of identifying the most beneficial approach for managing brain metastases.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with five or more brain metastases from a non-hematopoietic malignancy, and who meet specific health criteria.

Not a fit: Patients with fewer than five brain metastases or those with hematopoietic malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with brain metastases, potentially improving survival and quality of life.

How similar studies have performed: Previous studies have shown promising results with stereotactic radiosurgery, but this specific comparison with HA-WBRT and memantine is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Tucson, Arizona and 85 other locations

+36 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Brain Metastases
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.