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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03550391
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Canadian Cancer Trials Group
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	David RobergeMichael ChanVina Gondi
Principal Investigator Affiliation	CHUM-Centre Hospitalier de l'Universite de MontrealWake Forest School of Medicine, Winston-Salem, NCNorthwestern Medicine Cancer Center, Warrenville IL
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Canada, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Metastases

Additional Details

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).

Arms & Interventions

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

Drug: - 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:

Radiation: - Hippocampal-avoidant (HA-WBRT) Radiotherapy

30Gy in 10 fractions

Procedure: - Stereotactic Radiosurgery (SRS)

18-20 or 22 Gy in single fraction

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Tucson, Arizona

Status

Recruiting

Address

University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, 85704

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