Testing the Addition of Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in People With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery

January 9, 2024 updated by: NRG Oncology

Phase III Trial of Salvage Stereotactic Radiosurgery (SRS) or SRS + Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for First or Second Distant Brain Relapse After Upfront SRS With Brain Metastasis Velocity >/= 4 Brain Metastases/Year

This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone in treating patients with cancer that has spread to the brain and come back in other areas of the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain radiation therapy decreases the amount of radiation that is delivered to the hippocampus, which is a brain structure that is important for memory. The medicine memantine is also often given with whole brain radiation therapy because it may decrease the risk of side effects of radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation only to the small areas of cancer in the brain and avoids the surrounding normal brain tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread to the brain and returned in other areas of the brain after receiving stereotactic radiosurgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if salvage stereotactic radiosurgery (SRS) plus whole brain radiotherapy with hippocampal avoidance (HA-WBRT) in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS prolongs time to neurologic death as compared to salvage SRS alone.

SECONDARY OBJECTIVES:

I. To determine if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS prolongs overall survival as compared to salvage SRS alone.

II. To evaluate if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS prolongs intracranial progression-free survival as compared to salvage SRS alone.

III. To evaluate if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS improves brain metastasis velocity at subsequent relapse as compared to salvage SRS alone.

IV. To assess perceived difficulties in cognitive abilities, symptom burden and health status after salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS.

V. To compare neurocognitive function outcomes following salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS.

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 salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS improves brain metastasis velocity and/or overall survival at subsequent relapse as compared to salvage SRS.

VI. To compare the estimated cost of brain-related therapies and quality-adjusted life years in patients who receive salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS.

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. Within 1 week prior to or following HA-WBRT, patients undergo salvage SRS. 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.

ARM II: Patients undergo salvage SRS.

After completion of study treatment, patients are followed up every 2-3 months for at least 1 year.

Study Type

Interventional

Enrollment (Estimated)

350

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • Banner University Medical Center - Tucson
        • Contact:
        • Principal Investigator:
          • Charles C. Hsu
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • University of Arizona Cancer Center-North Campus
        • Contact:
        • Principal Investigator:
          • Charles C. Hsu
    • California
      • Corona, California, United States, 92879
        • Recruiting
        • City of Hope Corona
        • Contact:
        • Principal Investigator:
          • Trevor D. Lim
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Trevor D. Lim
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope at Irvine Lennar
        • Contact:
          • Site Public Contact
          • Phone Number: 877-467-3411
        • Principal Investigator:
          • Trevor D. Lim
      • Lancaster, California, United States, 93534
        • Recruiting
        • City of Hope Antelope Valley
        • Contact:
        • Principal Investigator:
          • Trevor D. Lim
      • Roseville, California, United States, 95661
        • Recruiting
        • Sutter Cancer Centers Radiation Oncology Services-Roseville
        • Principal Investigator:
          • Christopher U. Jones
        • Contact:
      • Roseville, California, United States, 95661
      • Sacramento, California, United States, 95816
      • South Pasadena, California, United States, 91030
        • Recruiting
        • City of Hope South Pasadena
        • Contact:
        • Principal Investigator:
          • Trevor D. Lim
      • Torrance, California, United States, 90503
        • Recruiting
        • City of Hope South Bay
        • Contact:
          • Site Public Contact
          • Phone Number: 877-467-3411
        • Principal Investigator:
          • Trevor D. Lim
      • Upland, California, United States, 91786
        • Recruiting
        • City of Hope Upland
        • Contact:
        • Principal Investigator:
          • Trevor D. Lim
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19713
        • Suspended
        • Delaware Clinical and Laboratory Physicians PA
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants PA
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19718
        • Recruiting
        • Christiana Care Health System-Christiana Hospital
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
    • Florida
      • Coral Gables, Florida, United States, 33146
        • Active, not recruiting
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • Active, not recruiting
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Jacksonville, Florida, United States, 32224-9980
        • Completed
        • Mayo Clinic in Florida
      • Miami, Florida, United States, 33136
        • Active, not recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Pembroke Pines, Florida, United States, 33028
        • Recruiting
        • Memorial Hospital West
        • Contact:
          • Site Public Contact
          • Phone Number: 954-265-4325
        • Principal Investigator:
          • Michael J. Burdick
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Principal Investigator:
          • Ken Tatebe
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Principal Investigator:
          • Steven J. Chmura
        • Contact:
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Rimas V. Lukas
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Contact:
        • Principal Investigator:
          • Rimas V. Lukas
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Contact:
        • Principal Investigator:
          • Rimas V. Lukas
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • The Carle Foundation Hospital
        • Contact:
        • Principal Investigator:
          • Kalika P. Sarma
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Contact:
        • Principal Investigator:
          • Rimas V. Lukas
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Recruiting
        • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 443-777-7364
        • Principal Investigator:
          • Stephen K. Ronson
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Mark V. Mishra
      • Bel Air, Maryland, United States, 21014
        • Recruiting
        • UM Upper Chesapeake Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 443-643-3010
        • Principal Investigator:
          • Matthew J. Ferris
      • Columbia, Maryland, United States, 21044
        • Recruiting
        • Central Maryland Radiation Oncology in Howard County
        • Contact:
          • Site Public Contact
          • Phone Number: 443-546-1300
        • Principal Investigator:
          • Mark V. Mishra
      • Glen Burnie, Maryland, United States, 21061
        • Recruiting
        • UM Baltimore Washington Medical Center/Tate Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 410-553-8100
        • Principal Investigator:
          • Mark V. Mishra
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Suspended
        • Saint Joseph Mercy Hospital
      • Brighton, Michigan, United States, 48114
        • Suspended
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
      • Chelsea, Michigan, United States, 48118
        • Suspended
        • Saint Joseph Mercy Chelsea
      • Chelsea, Michigan, United States, 48118
        • Suspended
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
      • Ypsilanti, Michigan, United States, 48197
        • Suspended
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Active, not recruiting
        • University of Mississippi Medical Center
    • Missouri
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Contact:
        • Principal Investigator:
          • Christopher D. Abraham
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Christopher D. Abraham
      • Saint Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Contact:
        • Principal Investigator:
          • Christopher D. Abraham
      • Saint Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Contact:
        • Principal Investigator:
          • Christopher D. Abraham
      • Saint Peters, Missouri, United States, 63376
        • Recruiting
        • Siteman Cancer Center at Saint Peters Hospital
        • Contact:
        • Principal Investigator:
          • Christopher D. Abraham
    • New York
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health/Center for Advanced Medicine
        • Principal Investigator:
          • Anuj Goenka
        • Contact:
          • Site Public Contact
          • Phone Number: 516-734-8896
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Principal Investigator:
          • Yuhchyau Chen
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Principal Investigator:
          • Michael D. Chan
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
      • Fargo, North Dakota, United States, 58122
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Sasha J. Beyer
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Tyler Gunter
    • Pennsylvania
      • Chadds Ford, Pennsylvania, United States, 19317
        • Recruiting
        • Christiana Care Health System-Concord Health Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Medical Center
        • Contact:
        • Principal Investigator:
          • Heath B. Mackley
      • Greensburg, Pennsylvania, United States, 15601
        • Active, not recruiting
        • UPMC Cancer Centers - Arnold Palmer Pavilion
      • Lewisburg, Pennsylvania, United States, 17837
        • Recruiting
        • Geisinger Medical Oncology-Lewisburg
        • Contact:
        • Principal Investigator:
          • Heath B. Mackley
      • Media, Pennsylvania, United States, 19063
        • Suspended
        • Riddle Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Withdrawn
        • Thomas Jefferson University Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • Active, not recruiting
        • UPMC-Shadyside Hospital
      • Pottsville, Pennsylvania, United States, 17901
        • Recruiting
        • Geisinger Cancer Services-Pottsville
        • Contact:
        • Principal Investigator:
          • Heath B. Mackley
      • Willow Grove, Pennsylvania, United States, 19090
        • Withdrawn
        • Asplundh Cancer Pavilion
      • Wynnewood, Pennsylvania, United States, 19096
        • Recruiting
        • Lankenau Medical Center
        • Contact:
        • Principal Investigator:
          • Albert S. DeNittis
      • York, Pennsylvania, United States, 17408
        • Active, not recruiting
        • UPMC Memorial
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Charlotte Rivers
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Cancer Institute - Faris
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Emory McTyre
    • Texas
      • Lubbock, Texas, United States, 79410
        • Recruiting
        • Covenant Medical Center-Lakeside
        • Contact:
        • Principal Investigator:
          • Gabriel Axelrud
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Active, not recruiting
        • Virginia Commonwealth University/Massey Cancer Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Active, not recruiting
        • West Virginia University Healthcare
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-622-8922
        • Principal Investigator:
          • Andrew M. Baschnagel
      • Menomonee Falls, Wisconsin, United States, 53051
        • Recruiting
        • Froedtert Menomonee Falls Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 262-257-5100
        • Principal Investigator:
          • Michael W. Straza
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-3666
        • Principal Investigator:
          • Michael W. Straza
      • Oak Creek, Wisconsin, United States, 53154
        • Recruiting
        • Drexel Town Square Health Center
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
        • Principal Investigator:
          • Michael W. Straza
      • West Bend, Wisconsin, United States, 53095
        • Recruiting
        • Froedtert West Bend Hospital/Kraemer Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
        • Principal Investigator:
          • Michael W. Straza

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have developed their first or second distant brain relapse(s) at least 8 weeks after upfront SRS and within 21 days prior to randomization

    • 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 magnetic resonance imaging (MRI) brain scan obtained within 21 days prior to randomization

    • 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 upfront 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 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
  • 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:

  • 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, small cell carcinoma, 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-aspartate (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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (salvage SRS, 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. Within 1 week prior to or following HA-WBRT, patients undergo salvage SRS. 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.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Memantine
Given PO
Radiation: Stereotactic Radiosurgery
Undergo salvage SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
Radiation: Whole-Brain Radiotherapy
Undergo HA-WBRT
Other Names:
  • WBRT
  • whole-brain radiation therapy
Active Comparator: Arm II (salvage SRS)
Patients undergo salvage SRS.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Radiation: Stereotactic Radiosurgery
Undergo salvage SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Neurologic Death
Time Frame: From randomization until progressive neurologic decline at time of death, irrespective of status of extracranial disease, or death from inter-current disease in patients with severe neurologic dysfunction, assessed up to 3 years
The primary comparison of treatment effect on neurologic deaths will be based a one-sided 0.05-level (score) test for cause-specific hazard ratio in a Cox proportional hazards model. Additional analyses will involve estimating the median time to neurologic death using the cumulative incidence function estimator in the presence of precluding events such as non-neurologic deaths in the two arms, separately. The Gray's test will be used to evaluate the difference in the distribution of neurologic deaths. These results will be interpreted in light of the competing non-neurologic deaths, which may be frequent.
From randomization until progressive neurologic decline at time of death, irrespective of status of extracranial disease, or death from inter-current disease in patients with severe neurologic dysfunction, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From randomization to death from any cause, assessed up to 3 years
Analysis will consist of estimation of the OS curves via the Kaplan-Meier method and a stratified log-rank test. Additional analyses may consist of estimating the hazard ratio via the Cox proportional hazards model, accounting for other prognostic covariates (and evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying), and evaluating for potential treatment by prognostic covariate interactions.
From randomization to death from any cause, assessed up to 3 years
Intracranial Progression-Free Survival (IPFS)
Time Frame: From randomization to intracranial progression or death from any cause, assessed up to 3 years
Analysis will consist of estimation of the IPFS curves via the Kaplan-Meier method and a stratified log-rank test. Additional analyses may consist of estimating the hazard ratio via the Cox proportional hazards model, accounting for other prognostic covariates (and evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying), and evaluating for potential treatment by prognostic covariate interactions.
From randomization to intracranial progression or death from any cause, assessed up to 3 years
Brain Metastasis Velocity (BMV) at subsequent relapse
Time Frame: Up to 3 years
The Wilcoxon rank-sum test will be used to compare the distributions of BMVs between the two treatment arms at 2-sided 0.05 level.
Up to 3 years
Cognitive Abilities
Time Frame: Up to 1 year
Measured by the Patient Reported Outcomes Measurement Information System Cognitive Function Short Form 4a version 2.0.
Up to 1 year
Symptom Burden
Time Frame: Up to 1 year
Measured by the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT). The MDASI-BT rates symptoms on an 11- point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours.
Up to 1 year
Health Status
Time Frame: Up to 1 year
Measured by the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L). The EQ-5D-5L uses 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems) to assess current health status.
Up to 1 year
Incidence of Adverse Events associated with the interventions
Time Frame: Up to 3 years
Adverse Events (AEs) will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arm.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Vinai Gondi, NRG Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2020

Primary Completion (Estimated)

January 31, 2025

Study Completion (Estimated)

January 31, 2030

Study Registration Dates

First Submitted

October 7, 2020

First Submitted That Met QC Criteria

October 13, 2020

First Posted (Actual)

October 19, 2020

Study Record Updates

Last Update Posted (Actual)

January 10, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-BN009 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2020-07375 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Renal Cell Carcinoma

Clinical Trials on Quality-of-Life Assessment

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo, DR of

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe