Breast Cancer Clinical Trial

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

Summary

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.

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Full 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.

View Eligibility Criteria

Eligibility Criteria

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 is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

350

Study ID:

NCT04588246

Recruitment Status:

Recruiting

Sponsor:

NRG Oncology

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There are 45 Locations for this study

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Banner University Medical Center - Tucson
Tucson Arizona, 85719, United States More Info
Site Public Contact
Contact
[email protected]
Charles C. Hsu
Principal Investigator
University of Arizona Cancer Center-North Campus
Tucson Arizona, 85719, United States More Info
Site Public Contact
Contact
800-327-2873
Charles C. Hsu
Principal Investigator
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables Florida, 33146, United States More Info
Site Public Contact
Contact
305-243-2647
Eric A. Mellon
Principal Investigator
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach Florida, 33442, United States More Info
Site Public Contact
Contact
305-243-2647
Eric A. Mellon
Principal Investigator
Mayo Clinic in Florida
Jacksonville Florida, 32224, United States More Info
Site Public Contact
Contact
855-776-0015
Jennifer L. Peterson
Principal Investigator
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami Florida, 33136, United States More Info
Site Public Contact
Contact
305-243-2647
Eric A. Mellon
Principal Investigator
Memorial Hospital West
Pembroke Pines Florida, 33028, United States More Info
Site Public Contact
Contact
954-265-4325
Michael J. Burdick
Principal Investigator
Northwestern University
Chicago Illinois, 60611, United States More Info
Site Public Contact
Contact
312-695-1301
[email protected]
Rimas V. Lukas
Principal Investigator
Carle on Vermilion
Danville Illinois, 61832, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Kalika P. Sarma
Principal Investigator
Northwestern Medicine Cancer Center Kishwaukee
DeKalb Illinois, 60115, United States More Info
Site Public Contact
Contact
630-352-5360
[email protected]
Vinai Gondi
Principal Investigator
Carle Physician Group-Effingham
Effingham Illinois, 62401, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Kalika P. Sarma
Principal Investigator
Northwestern Medicine Cancer Center Delnor
Geneva Illinois, 60134, United States More Info
Site Public Contact
Contact
630-352-5360
[email protected]
Vinai Gondi
Principal Investigator
Carle Physician Group-Mattoon/Charleston
Mattoon Illinois, 61938, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Kalika P. Sarma
Principal Investigator
Carle Cancer Center
Urbana Illinois, 61801, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Kalika P. Sarma
Principal Investigator
The Carle Foundation Hospital
Urbana Illinois, 61801, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Kalika P. Sarma
Principal Investigator
Northwestern Medicine Cancer Center Warrenville
Warrenville Illinois, 60555, United States More Info
Site Public Contact
Contact
630-352-5360
[email protected]
Vinai Gondi
Principal Investigator
University of Maryland/Greenebaum Cancer Center
Baltimore Maryland, 21201, United States More Info
Site Public Contact
Contact
800-888-8823
Mark V. Mishra
Principal Investigator
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore Maryland, 21237, United States More Info
Site Public Contact
Contact
443-777-7364
Kamila Nowak Choi
Principal Investigator
UM Upper Chesapeake Medical Center
Bel Air Maryland, 21014, United States More Info
Site Public Contact
Contact
443-643-3010
Matthew J. Ferris
Principal Investigator
Central Maryland Radiation Oncology in Howard County
Columbia Maryland, 21044, United States More Info
Site Public Contact
Contact
443-546-1300
Mark V. Mishra
Principal Investigator
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie Maryland, 21061, United States More Info
Site Public Contact
Contact
410-553-8100
Mark V. Mishra
Principal Investigator
Tufts Medical Center
Boston Massachusetts, 02111, United States More Info
Site Public Contact
Contact
617-636-5000
[email protected]
John E. Mignano
Principal Investigator
Saint Joseph Mercy Hospital
Ann Arbor Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton Michigan, 48114, United States
Saint Joseph Mercy Chelsea
Chelsea Michigan, 48118, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea Michigan, 48118, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti Michigan, 48197, United States
University of Mississippi Medical Center
Jackson Mississippi, 39216, United States
Siteman Cancer Center at West County Hospital
Creve Coeur Missouri, 63141, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Christopher D. Abraham
Principal Investigator
Washington University School of Medicine
Saint Louis Missouri, 63110, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Christopher D. Abraham
Principal Investigator
Siteman Cancer Center-South County
Saint Louis Missouri, 63129, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Christopher D. Abraham
Principal Investigator
Siteman Cancer Center at Christian Hospital
Saint Louis Missouri, 63136, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Christopher D. Abraham
Principal Investigator
Siteman Cancer Center at Saint Peters Hospital
Saint Peters Missouri, 63376, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Christopher D. Abraham
Principal Investigator
Sanford Bismarck Medical Center
Bismarck North Dakota, 58501, United States More Info
Site Public Contact
Contact
701-323-5760
[email protected]
Preston D. Steen
Principal Investigator
Sanford Broadway Medical Center
Fargo North Dakota, 58122, United States More Info
Site Public Contact
Contact
701-323-5760
[email protected]
Preston D. Steen
Principal Investigator
Sanford Roger Maris Cancer Center
Fargo North Dakota, 58122, United States More Info
Site Public Contact
Contact
701-234-6161
[email protected]
Preston D. Steen
Principal Investigator
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States More Info
Site Public Contact
Contact
405-271-8777
[email protected]
Tyler Gunter
Principal Investigator
Geisinger Medical Center
Danville Pennsylvania, 17822, United States More Info
Site Public Contact
Contact
570-271-5251
[email protected]
Heath B. Mackley
Principal Investigator
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg Pennsylvania, 15601, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg Pennsylvania, 17837, United States More Info
Site Public Contact
Contact
570-374-8555
[email protected]
Heath B. Mackley
Principal Investigator
Thomas Jefferson University Hospital
Philadelphia Pennsylvania, 19107, United States More Info
Site Public Contact
Contact
215-600-9151
[email protected]
Scott H. Herbert
Principal Investigator
UPMC-Shadyside Hospital
Pittsburgh Pennsylvania, 15232, United States
Geisinger Cancer Services-Pottsville
Pottsville Pennsylvania, 17901, United States More Info
Site Public Contact
Contact
800-275-6401
[email protected]
Heath B. Mackley
Principal Investigator
Asplundh Cancer Pavilion
Willow Grove Pennsylvania, 19090, United States More Info
Site Public Contact
Contact
215-600-9151
[email protected]
Scott H. Herbert
Principal Investigator
UPMC Memorial
York Pennsylvania, 17408, United States
Prisma Health Cancer Institute - Faris
Greenville South Carolina, 29605, United States More Info
Site Public Contact
Contact
864-241-6251
Emory McTyre
Principal Investigator
Virginia Commonwealth University/Massey Cancer Center
Richmond Virginia, 23298, United States More Info
Site Public Contact
Contact
[email protected]
Timothy J. Harris
Principal Investigator
West Virginia University Healthcare
Morgantown West Virginia, 26506, United States
Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States More Info
Site Public Contact
Contact
414-805-3666
Joseph A. Bovi
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

350

Study ID:

NCT04588246

Recruitment Status:

Recruiting

Sponsor:


NRG Oncology

How clear is this clinincal trial information?

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