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

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join 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 be able to join 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).
• 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

• University of Arizona Cancer Center-Orange Grove Campus, Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus, Tucson, Arizona, United States
• City of Hope Corona, Corona, California, United States
• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• City of Hope at Irvine Lennar, Irvine, California, United States
• UC San Diego Moores Cancer Center, La Jolla, California, United States
• City of Hope Antelope Valley, Lancaster, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, California, United States
• Kaiser Permanente-Rancho Cordova Cancer Center, Rancho Cordova, California, United States
• Rohnert Park Cancer Center, Rohnert Park, California, United States
• The Permanente Medical Group-Roseville Radiation Oncology, Roseville, California, United States
• South Sacramento Cancer Center, Sacramento, California, United States

+ 74 more sites.

Who to contact

Chris O'Callaghan · 613-533-6430 · cocallaghan@ctg.queensu.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT03550391.