Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5-15 Brain Metastases
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03550391|
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : May 12, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain Metastases||Drug: Memantine Radiation: Hippocampal-avoidant (HA-WBRT) Radiotherapy Procedure: Stereotactic Radiosurgery (SRS)||Phase 3|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||206 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||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|
|Masking:||None (Open Label)|
|Official Title:||A Phase III Trial of Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5-15 Brain Metastases|
|Actual Study Start Date :||May 25, 2018|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||June 30, 2023|
Experimental: Hippocampal-avoidant (HA-WBRT) plus Memantine
WBRT 30Gy in 10 fractions + 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
Experimental: Stereotactic Radiosurgery (SRS)
SRS 18-20 or 22Gy in single fraction
Procedure: Stereotactic Radiosurgery (SRS)
18-20 or 22 Gy in single fraction
- Overall Survival [ Time Frame: 4.5 years ]To compare the overall survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine
- Neurocognitive progression-free survival [ Time Frame: 4.5 years ]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
- Time to central nervous system (CNS) failure (local, distant, and leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine [ Time Frame: 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 [ Time Frame: 4.5 years ]
- Number of salvage procedures following SRS in comparison to HA-WBRT + memantine [ Time Frame: 4.5 years ]
- Neurocognitive progression-free survival in patients who receive SRS compared to HA-WBRT + memantine [ Time Frame: 4.5 years ]measured from date the patient is randomized to date at which there is a drop of at least 1.5 standard deviations from baseline in two of the six neurocognitive tests (all tests are standardized based on published norms)
- Tabulate and descriptively compare the post-treatment adverse events associated with the interventions. [ Time Frame: 4.5 years ]
- Time delay to (re-)initiation of systemic therapy in patients receiving SRS in comparison to HA-WBRT + memantine [ Time Frame: 4.5 years ]
- Prospectively validate a predictive nomogram for distant brain failure in patients who receive SRS [ Time Frame: 4.5 years ]a predictive nomogram as a clinically useful tool to determine the likelihood of distant brain failure (DBF) at different time points after radiosurgery
- Compare the estimated cost of brain-related therapies in patients who receive SRS compared to patients who receive HA-WBRT + memantine. [ Time Frame: 4.5 years ]Comparison based on payer rates (Medicare for US / provincial heath authorities in Canadian jurisdictions with activity-based funding)
- Quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) with brain cancer module (BN20) [ Time Frame: 4.5 years ]
- Quality of life assessed by ECOG performance status [ Time Frame: 4.5 years ]
- Quality of life, as assessed by EQ-5D-5L [ Time Frame: 4.5 years ]
- Collect plasma to evaluate whether detectable somatic mutations in liquid biopsy can enhance prediction of the overall survival and development of new brain metastases. [ Time Frame: 4.5 years ]
- Analysis of serum samples for inflammatory biomarker C-reactive protein and brain-derived-neurotrophic factor (BDNF) to elucidate molecular/genomic mechanisms of neurocognitive decline and associated radiographic changes [ Time Frame: 4.5 years ]
- Collect whole-brain dosimetry in SRS patients to be prospectively correlated with cognitive toxicity, intracranial control and radiation necrosis [ Time Frame: 4.5 years ]
- Evaluate serial changes in imaging features found in routine MRI images (T2w changes, morphometry) that may predict tumour control and/or neurocognitive outcomes [ Time Frame: 4.5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03550391
|Contact: Chris O'Callaghanemail@example.com|
|Study Chair:||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|