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Clinical Trials in Canada / NCT04804644
Active, not recruiting Phase 3

Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability

NCT04804644 · tracked via the Priya Life Science Canada tracker
Phase
Phase 3
Started
2021-06-08
Last updated
2026-09-14

Condition(s) studied

Metastatic Lung Small Cell CarcinomaMetastatic Malignant Neoplasm in the BrainRecurrent Lung Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Investigational drug(s) / intervention(s)

Biospecimen CollectionMagnetic Resonance ImagingMemantine HydrochlorideNeurocognitive AssessmentStereotactic RadiosurgerySurvey AdministrationWhole-Brain Radiotherapy

Biospecimen Collection: Undergo blood sample collection

Magnetic Resonance Imaging: Undergo MRI

Memantine Hydrochloride: Given PO

Neurocognitive Assessment: Ancillary studies

Stereotactic Radiosurgery: Undergo SRS

Survey Administration: Ancillary studies

Whole-Brain Radiotherapy: Undergo HA-WBRT

Study summary

This phase III trial compares the effect of stereotactic radiosurgery to standard of care memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of the brain) for the treatment of small cell lung cancer that has spread to the brain. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole brain radiation therapy delivers a low dose of radiation to the entire brain including the normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT) decreases the amount of radiation that is delivered to the hippocampus which is a brain structure that is important for memory. The drug, memantine, is also often given with whole brain radiotherapy because it may decrease the risk of side effects related to thinking and memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking compared to standard of care HA-WBRT plus memantine.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * Pathologically (histologically or cytologically) proven diagnosis of small cell lung cancer within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic or brain metastasis); * Patients with de novo or recurrent small cell lung cancer are permitted. * Brain metastases =\< 4 cm in largest diameter and outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =\< 21 days prior to study entry. * The total tumor volume must be 30 cm\^3 or less. Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumor volume. * Brain metastases can be diagnosed synchronous to the initial diagnosis of small cell lung cancer or metachronous to the initial diagnosis and management of small cell lung cancer. * Brain metastases must be diagnosed on MRI, which will include the following elements: * REQUIRED MRI ELEMENTS * Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm. * Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged). * A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required. This can be acquired as a two dimensional (2D) or 3D image. If 2D, the images should be obtained in the axial plane. * ADDITIONAL RECOMMENDATIONS * Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence. * Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1. * Recommendation is that imaging be performed on a 3 Tesla (3T) MRI. * Recommendation is that the study participants be scanned on the same MRI instrument at each time point. * Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020. * If additional sequences are obtained, total imaging time should not exceed 60 minutes. * If additional metastases not known at the time of registration/randomization or seen in the MRI used for eligibility are subsequently found on the radiation therapy (RT) planning MRI such that the total intacranial volume exceeds 30 cm\^3, the patient is still considered eligible. * History/physical examination * Age \>= 18 * Karnofsky performance status of \>= 70 * Creatinine clearance \>= 30 ml/min * Following the diagnosis of brain metastases, patients can initiate and treat with systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain metastases are asymptomatic and not located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment, brain MRI must be repeated to confirm eligibility. * Patients with symptomatic brain metastases and/or brain metastases in eloquent locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible for enrollment on the trial; however, the specific treatment approach of starting with systemic therapy alone and delaying brain radiation is not recommended for these patients. * Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted. * Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to registration. Women of childbearing potential and men who are sexually active must use contraception while on study. * Patients may have had prior intracranial surgical resection. * Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian. * The patient must provide study-specific informed consent prior to study entry. * Patients with impaired decision-making capacity are not permitted on study. * ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION * The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2. * NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration. * PRIOR TO STEP 2 REGISTRATION: The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2. NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration. Exclusion Criteria: * Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is permitted. * For patients receiving fractionated SRS on an every-other-day basis, planned infusion of cytotoxic chemotherapy is not permitted between SRS treatments. * Brainstem metastasis \> 10 cm\^3 * Prior allergic reaction to memantine. * Patients with definitive leptomeningeal metastases. * Known history of demyelinating disease such as multiple sclerosis. * Contraindication to MR imaging such as implanted metal devices that are MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions regarding MRI compatibility of implanted objects should be reviewed with the Radiology Department performing the MRI). * Current use of (other N-methyl-D-aspartate \[NMDA\] antagonists) amantadine, ketamine, or dextromethorphan. * Radiographic evidence of hydrocephalus or other architectural change of the ventricular system resulting in significant anatomic distortion of the hippocampus, including placement of external ventricular drain or ventriculoperitoneal shunt. * Mild cases of hydrocephalus not resulting in significant anatomic distortion of the hippocampus are permitted. * Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial irradiation (PCI).

Primary outcome measure(s)

Trial sites (231)

FacilityCityRegionStatus
Mayo Clinic Hospital in Arizona Phoenix Arizona
Kaiser Permanente-Anaheim Anaheim California
Kaiser Permanente-Bellflower Bellflower California
Kaiser Permanente Los Angeles Medical Center Los Angeles California
Los Angeles General Medical Center Los Angeles California
USC / Norris Comprehensive Cancer Center Los Angeles California
Kaiser Permanente-Ontario Ontario California
UCHealth University of Colorado Hospital Aurora Colorado
UCHealth Memorial Hospital Central Colorado Springs Colorado
Memorial Hospital North Colorado Springs Colorado
Smilow Cancer Hospital Care Center at Greenwich Greenwich Connecticut
Smilow Cancer Hospital Care Center - Guilford Guilford Connecticut
Smilow Cancer Center/Yale-New Haven Hospital New Haven Connecticut
Yale University New Haven Connecticut
Smilow Cancer Hospital Care Center-Trumbull Trumbull Connecticut
Smilow Cancer Hospital Care Center - Waterford Waterford Connecticut
Beebe Medical Center Lewes Delaware
Delaware Clinical and Laboratory Physicians PA Newark Delaware
Helen F Graham Cancer Center Newark Delaware
Medical Oncology Hematology Consultants PA Newark Delaware
Christiana Care Health System-Christiana Hospital Newark Delaware
Beebe Health Campus Rehoboth Beach Delaware
Christiana Care Health System-Wilmington Hospital Wilmington Delaware
UM Sylvester Comprehensive Cancer Center at Coral Gables Coral Gables Florida
UM Sylvester Comprehensive Cancer Center at Deerfield Beach Deerfield Beach Florida
UF Health Cancer Institute - Gainesville Gainesville Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
Moffitt Cancer Center-International Plaza Tampa Florida
Moffitt Cancer Center - McKinley Campus Tampa Florida
Moffitt Cancer Center Tampa Florida
Moffitt Cancer Center at Wesley Chapel Wesley Chapel Florida
Emory University Hospital Midtown Atlanta Georgia
Emory University Hospital/Winship Cancer Institute Atlanta Georgia
Emory Saint Joseph's Hospital Atlanta Georgia
Northside Hospital Atlanta Georgia
Northside Hospital-Cherokee Canton Georgia
Northside Hospital-Forsyth Cumming Georgia
Memorial Health University Medical Center Savannah Georgia
Rush-Copley Medical Center Aurora Illinois
Centralia Oncology Clinic Centralia Illinois

+ 191 more sites — see the full list on the official registry below.

More NRG Oncology trials in Canada

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04804644 on ClinicalTrials.gov ↗ ← All trials in Canada