Comparing Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in Patients With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
NCT ID: NCT04588246
Last Updated: 2025-06-06
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
19 participants
INTERVENTIONAL
2021-08-05
2024-08-06
Brief Summary
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Detailed Description
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I. To determine if hippocampal-avoidant plus whole brain radiotherapy (HA-WBRT) in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year prolongs time to neurologic death as compared to stereotactic radiosurgery (SRS).
SECONDARY OBJECTIVES:
I. To determine if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year prolongs overall survival as compared to SRS.
II. To evaluate if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year prolongs intracranial progression-free survival as compared to SRS.
III. To evaluate if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year improves brain metastasis velocity at subsequent relapse as compared to SRS.
IV. To assess perceived difficulties in cognitive abilities, symptom burden and health status after HA-WBRT, as compared to SRS, in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year.
V. To compare neurocognitive function outcomes following HA-WBRT, as compared to SRS, in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year.
VI. To tabulate and descriptively compare the adverse events associated with the interventions.
VII. To tabulate and descriptively compare the number of salvage procedures used to manage recurrent intracranial disease following the interventions.
EXPLORATORY OBJECTIVES:
I. To collect serum, plasma, and whole blood for translational research analyses.
II. To collect baseline and all follow-up magnetic resonance (MR) imaging for hippocampal volume, memory center substructures, axial T2 volumes, and quantitative texture analysis.
III. To collect baseline and follow-up MR imaging to extract whole brain volume, white matter volume and volume of metastatic disease to correlate with cognitive change at 4 months.
IV. To evaluate dose-volume histogram parameters to correlate with radiation toxicity.
V. To assess in patients receiving immunotherapy or targeted therapy, if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year at time improves brain metastasis velocity and/or overall survival at subsequent relapse as compared to SRS.
VI. To compare the estimated cost of brain-related therapies and quality-adjusted life years in patients who receive HA-WBRT, as compared to SRS, in patients with distant brain failure with metastasis velocity \>= 4 new brain metastases/year.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo HA-WBRT daily (5 times weekly) for 2 weeks for a total of 10 fractions in the absence of disease progression or unacceptable toxicity. Prior to HA-WBRT or no later than the 4th treatment, patients also receive memantine orally (PO) once daily (QD) or twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) and may undergo blood sample collection throughout the trial.
ARM II: Patients undergo single fraction SRS or fractionated SRS (fSRS) on study. Patients also undergo CT and MRI and may undergo blood sample collection throughout the trial.
Patients are followed up at 2, 4, 6, 9, and 12 months from the start of SRS/fSFS or HA-WBRT and then every 6 months after month 12 and within 21 days after patient death.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Arm I (memantine, HA-WBRT)
Patients undergo HA-WBRT daily (5 times weekly) for 2 weeks for a total of 10 fractions in the absence of disease progression or unacceptable toxicity. Prior to HA-WBRT or no later than the 4th treatment, patients also receive memantine PO QD or BID for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI and may undergo blood sample collection throughout the trial.
Biospecimen Collection
Undergo blood sample collection
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Memantine
Given PO
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Whole-Brain Radiotherapy
Undergo HA-WBRT
Arm II (SRS/fSRS)
Patients undergo single fraction SRS or fSRS on study. Patients also undergo CT and MRI and may undergo blood sample collection throughout the trial.
Biospecimen Collection
Undergo blood sample collection
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Stereotactic Radiosurgery
Undergo SRS/fSRS
Interventions
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Biospecimen Collection
Undergo blood sample collection
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Memantine
Given PO
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Stereotactic Radiosurgery
Undergo SRS/fSRS
Whole-Brain Radiotherapy
Undergo HA-WBRT
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Distant brain relapse lesions to be treated must measure =\< 3.0 cm in maximal extent and total volume of distant brain relapses to be treated must measure \< 30 mL on the contrast-enhanced diagnostic MRI brain scan obtained within 21 days prior to randomization
* "last SRS" refers to the most recent SRS procedure that the patient received prior to enrollment on this study
* Distant brain relapse lesions 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 fluid attenuated inversion recovery (FLAIR) (preferred) or T2 sequence is required. This can be acquired as a 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
* Brain metastasis velocity (BMV) since last SRS must be \>= 4 brain metastases/year
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* Pathologically (histologically or cytologically) proven diagnosis of small cell cancer, non-small cell lung cancer, melanoma, breast cancer, renal cell carcinoma, or gastrointestinal cancer within 10 years prior to randomization. If the original histologic proof of malignancy is greater than 10 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)
* Other histologies are not permitted
* History and physical examination within 28 days prior to randomization
* Age \>= 18
* Karnofsky performance status of \>= 70 within 28 days prior to randomization
* Calculated creatinine clearance (CrCl) \>= 30 ml/min (within 28 days prior to randomization)
* Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal (ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted) (within 28 days prior to randomization)
* Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to randomization
Exclusion Criteria
* Patients are permitted to have undergone multiple SRS treatments to different brain metastases so long as prior BMV has been less than 4 brain metastases/year
* Prior WBRT or prophylactic cranial irradiation
* Local relapse of metastasis previously treated with upfront SRS (i.e., relapse outside previously SRS-treated metastases is allowed)
* Brain metastases from primary germ cell tumor or lymphoma
* Definitive leptomeningeal metastasis
* Planned cytotoxic chemotherapy on the same day as SRS or HA-WBRT; concurrent immunotherapy is permitted
* Radiographic evidence of enlargement or other architectural distortion of the lateral ventricles, including placement of external ventricular drain or ventriculoperitoneal shunt
* Known history of demyelinating disease such as multiple sclerosis
* Inability to swallow pills
* Contraindication to MR imaging such as non-MR conditional implanted metal devices or unknown metallic foreign bodies, or contraindication to gadolinium contrast administration during MR imaging, such as anaphylactic allergy that cannot be adequately addressed with pre-contrast medications or acute kidney injury
* Contraindications to memantine, including:
* Allergy, including prior allergic reaction to memantine
* Intractable seizures on adequate anticonvulsive therapy-more than 1 seizure per month for the past 2 months
* Current use of N-methyl-D-asparatate (NMDA) agonist
* Current alcohol or drug abuse, which can exacerbate lethargy/dizziness with memantine
* Severe, active co-morbidity defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
* Transmural myocardial infarction within the last 6 months
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization
* Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of randomization
* Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease
* Renal tubular acidosis or metabolic acidosis
* Human immunodeficiency virus (HIV) positive with CD4 count \< 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 30 days prior to randomization. Note also that HIV testing is not required for eligibility for this protocol
* Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the medication and radiation involved in this study has unknown effects on the unborn fetus
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
NRG Oncology
OTHER
Responsible Party
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Principal Investigators
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Vinai Gondi
Role: PRINCIPAL_INVESTIGATOR
NRG Oncology
Locations
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Banner University Medical Center - Tucson
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
City of Hope Antelope Valley
Lancaster, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, United States
Sutter Roseville Medical Center
Roseville, California, United States
Sutter Medical Center Sacramento
Sacramento, California, United States
California Pacific Medical Center-Pacific Campus
San Francisco, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
City of Hope South Bay
Torrance, California, United States
City of Hope Upland
Upland, California, United States
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, United States
Helen F Graham Cancer Center
Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Memorial Hospital West
Pembroke Pines, Florida, United States
Northwestern University
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Carle at The Riverfront
Danville, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, United States
Carle Physician Group-Effingham
Effingham, Illinois, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
The Carle Foundation Hospital
Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, United States
UM Upper Chesapeake Medical Center
Bel Air, Maryland, United States
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland, United States
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, United States
Chelsea Hospital
Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
Northwell Health/Center for Advanced Medicine
Lake Success, New York, United States
University of Rochester
Rochester, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
Upstate Cancer Center at Verona
Verona, New York, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, United States
Sanford Broadway Medical Center
Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, United States
Riddle Memorial Hospital
Media, Pennsylvania, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, United States
Geisinger Cancer Services-Pottsville
Pottsville, Pennsylvania, United States
Lankenau Medical Center
Wynnewood, Pennsylvania, United States
UPMC Memorial
York, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, United States
Covenant Medical Center-Lakeside
Lubbock, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
West Virginia University Healthcare
Morgantown, West Virginia, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Drexel Town Square Health Center
Oak Creek, Wisconsin, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, United States
CHUM - Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada
Pamela Youde Nethersole Eastern Hospital
Chai Wan, , Hong Kong
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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NCI-2020-07375
Identifier Type: REGISTRY
Identifier Source: secondary_id
NRG-BN009
Identifier Type: -
Identifier Source: secondary_id
NRG-BN009
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-BN009
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-BN009
Identifier Type: -
Identifier Source: org_study_id
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