AzTrials
AzTrials

RadionecrosisPhase 2NCT02490878

Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases

A Phase 2 study testing bevacizumab and corticosteroids in people with Radionecrosis and Brain Metastases, run by Alliance for Clinical Trials in Oncology at 341 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized phase II study aims to investigate whether the addition of bevacizumab to standard corticosteroid therapy results in greater improvement in symptoms and less treatment-induced symptoms compared with standard corticosteroid therapy for patients with symptomatic brain radionecrosis following… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Radionecrosis, Brain Metastases
What is being tested?
bevacizumab and corticosteroids
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
19 participants
Where
341 sitesin 2 countries
Study dates
Apr 2016to 15 Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Pre-Registration Eligibility Criteria:

  1. Patients who present with symptomatic brain radionecrosis after they have received radiosurgery for brain metastases from primary solid tumor including but not limited to lung, breast, colorectal cancer but excluding melanoma, choriocarcinoma, renal cell carcinoma or gliomas
  2. Patients at institutions that elect to utilize central imaging review to confirm eligibility must be pre-registered prior to submission of these images; images should be submitted as soon as possible after the pre-registration magnetic resonance imaging (MRI) is obtained; turnaround time for this review will be =< 72 business hours after receipt of images by the Imaging and Radiation Oncology Core (IROC)
  3. Patients at institutions that elect to confirm eligibility locally may be pre-registered at the same time as they are randomized

Registration/Randomization Eligibility Criteria:

  1. A diagnosis of radionecrosis will be based on a clinical onset of symptoms and radiological findings of radionecrosis at 3-24 months following radiosurgery, with or without pathological confirmation. 1.1 'Symptomatic' brain radionecrosis to at least one lesion following radiosurgery treatment for brain metastases where 'symptomatic' is defined as: 1.1.1 New or increasing headache associated with mass effect, sensory or motor abnormality, cognitive changes, speech difficulty, balance or coordination difficulty, cranial nerve deficits 1.1.2 Symptoms are persistent or worsening despite administration of at least dexamethasone 4 mg (or equivalent corticosteroid) daily for 1 week 1.2 Clinical eligibility supported by central imaging real-time review. The presence of at least the following conventional MR image characteristic: 1.2.1 Conventional MR - Lesion quotient of < 0.3, where lesion quotient is defined as the proportional value of the maximum axial cross-sectional area of the T2-weighted defined lesion over the maximum axial cross-sectional area of the contrast-enhancing lesion on the T1-weighted post-gadolinium sequence on a comparable axial slice. If the conventional MR findings are not seen, the following dynamic susceptibility-contrast (DSC) MR characteristics may be used to meet eligibility for this study. 1.2.2 DSC MR - The cut-offs below will be based on GRE EPI DSC perfusion images, acquired without using a gadolinium pre-load: 1.2.2.1 Relative cerebral blood volume (rCBV) <1.5 in the enhancing- lesion relative to normal-appearing white matter (NAWM) 1.2.2.2. Percentage of signal recovery (PSR) > 76%, where PSR is determined by comparing the lower signal intensity during passage of the contrast bolus with the post-contrast signal intensity on the signal intensity-time curve 1.2.3 Centers that standardly use PET or MRS to determine a diagnosis of radionecrosis are permitted to use these modalities to assist in their patient selection; however the criteria described for conventional MR and/or DSC should also be met for study eligibility. Both PET and MRS are not mandatory for study eligibility.
  2. Prior to start of treatment 2.1 Must have been taking a stable dose of corticosteroids for symptom management for at least 1 week before baseline MRI. 2.2 No systemic therapy within 2 weeks prior to registration or plan for systemic therapy within the first 8 weeks after study registration. The protocol provides a list of 'approved systemic' therapies that are allowed for concurrent use with bevacizumab. 2.3 No bevacizumab ≤ 3 months of study registration. 2.4 Central imaging real-time review (72 hour turn around) to confirm eligibility.
  3. Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 14 days prior to registration and confirmation they are not nursing is required.
  4. Age ≥ 18 years
  5. Karnofsky Performance Status ≥ 60%
  6. Required Initial Laboratory Values ≤14 days of registration: 6.1 Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3 6.2 Platelet Count ≥ 100,000/mm3 6.3 Hemoglobin ≥ 10 g/dL* 6.3.1 allowing transfusion or other intervention to achieve this minimum hemoglobin 6.4 BUN < 30 mg/dL 6.5 Creatinine < 1.7 mg/dL 6.6 Bilirubin ≤ 2.0 mg/dL 6.7 ALT ≤ 3.0 x upper limits of normal (ULN) 6.8 AST ≤ 3.0 x ULN 6.9 INR <1.5 x ULN** 6.9.1 unless patients are receiving anti-coagulation therapy. Patients receiving anti-coagulation therapy with an agent such warfarin or heparin are allowed to participate if INR ≤ 3.0.** 6.10 UPC Ratio <0.5 or if ≥ 0.5 6.10.1 24-hour urine protein must be <1000 mg
  7. Able to participate in patient-report outcomes (MDASI-BT, DSQ-C, LASA) questionnaires. Assistance by research personnel is acceptable if participant has disabilities that make reading or writing difficult.
  8. No evidence of recent hemorrhage at pre-registration MRI of the brain, however the following are permitted: presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor.
  9. No excess risk of bleeding (any of the following): 9.1 Bleeding diathesis or coagulopathy 9.2 Thrombocytopenia 9.3 Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days or anticipation of need for major surgical procedure during the course of the study. 9.4 Minor surgical procedures, stereotactic biopsy, fine needle aspiration, or core biopsy within the past 7 days.
  10. No clinically significant cardiovascular disease. 10.1 No uncontrolled hypertension (systolic blood pressure ≤ 160 mm Hg or diastolic ≤ 100 mm Hg). Patients with hypertension must be adequately controlled with appropriate anti-hypertensive therapy or diet. 10.2 No history of arterial thrombotic events within the past 6 months, including: 10.2.1 transient ischemic attack (TIA) 10.2.2 cerebrovascular accident (CVA) 10.2.3 peripheral arterial thrombus 10.2.4 unstable angina or angina requiring surgical or medial intervention 10.2.5 myocardial infarction (MI) 10.2.6 significant peripheral artery disease (i.e., claudication on less than one block) 10.2.7 significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) 10.3 Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation. 10.4 No current New York Heart Association classification II, III, or IV congestive heart failure.
  11. No history of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within past 12 months.
  12. No central lung metastases with excessive active bleeding.
  13. No uncontrolled intercurrent illness including, but not limited to any of the following: ongoing or active infection requiring IV antibiotics, cardiac arrhythmia, or psychiatric illness and/or social situations that would limit compliance with study requirements.
  14. No history of serious non-healing wound, ulcer, or bone fractures.

Trial locations and contacts

341 sites in 2 countries.

309 sites in 2 countries

United States300 sites

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Cancer Care Center at Island Hospital

    Anacortes, Washington, 98221

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Ashland Memorial Medical Center

    Ashland, Wisconsin, 54806

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • University Cancer and Blood Center LLC

    Athens, Georgia, 30607

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • Saint Alphonsus Medical Center-Baker City

    Baker City, Oregon, 97814

  • Saint Louis Cancer and Breast Institute-Ballwin

    Ballwin, Missouri, 63011

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Boca Raton Regional Hospital

    Boca Raton, Florida, 33486

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Mountain States Tumor Institute

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Bozeman Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • United Hospital Center

    Bridgeport, West Virginia, 26330

  • IHA Hematology Oncology Consultants-Brighton

    Brighton, Michigan, 48114

  • Saint Joseph Mercy Brighton

    Brighton, Michigan, 48114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Cone Health Cancer Center at Alamance Regional

    Burlington, North Carolina, 27215

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • IHA Hematology Oncology Consultants-Canton

    Canton, Michigan, 48188

  • Saint Joseph Mercy Canton

    Canton, Michigan, 48188

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Roper Hospital

    Charleston, South Carolina, 29401

  • Charleston Hematology Oncology Associates-Roper

    Charleston, South Carolina, 29403

  • Lowcountry Hematology Oncology PA-North Charleston

    Charleston, South Carolina, 29406

  • Bon Secours Saint Francis Hospital

    Charleston, South Carolina, 29414

  • Charleston Hematology Oncology Associates PA-Saint Francis

    Charleston, South Carolina, 29414

  • Lowcountry Hematology Oncology PA-West Ashley

    Charleston, South Carolina, 29414

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • IHA Hematology Oncology Consultants-Chelsea

    Chelsea, Michigan, 48118

  • Saint Joseph Mercy Chelsea

    Chelsea, Michigan, 48118

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Oncology and Hematology Care Southeast

    Clackamas, Oregon, 97015

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Greenville Health System Cancer Institute-Laurens

    Clinton, South Carolina, 29325

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Medical Center

    Coeur d'Alene, Idaho, 83814

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Carle on Vermilion

    Danville, Illinois, 61832

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physicians LLC-Samaritan North

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Halifax Health Medical Center-Centers for Oncology

    Daytona Beach, Florida, 32114

  • Beaumont Hospital-Dearborn

    Dearborn, Michigan, 48124

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Ascension Saint John Hospital

    Detroit, Michigan, 48236

  • Essentia Health Saint Mary's - Detroit Lakes Clinic

    Detroit Lakes, Minnesota, 56501

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Greenville Health System Cancer Institute-Easley

    Easley, South Carolina, 29640

  • Great Lakes Cancer Management Specialists-Doctors Park

    East China Township, Michigan, 48054

  • Swedish Medical Center-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Englewood Hospital and Medical Center

    Englewood, New Jersey, 07631

  • Deaconess Clinic Downtown

    Evansville, Indiana, 47713

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Beaumont Hospital - Farmington Hills

    Farmington Hills, Michigan, 48336

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Genesee Cancer and Blood Disease Treatment Center

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Trinity Regional Medical Center

    Fort Dodge, Iowa, 50501

  • Essentia Health - Fosston

    Fosston, Minnesota, 56542

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Vanderbilt-Ingram Cancer Center Cool Springs

    Franklin, Tennessee, 37067

  • Saint Luke's Mountain States Tumor Institute - Fruitland

    Fruitland, Idaho, 83619

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Benefis Healthcare- Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • East Carolina University

    Greenville, North Carolina, 27834

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Greenville Health System Cancer Institute-Butternut

    Greenville, South Carolina, 29605

  • Greenville Health System Cancer Institute-Faris

    Greenville, South Carolina, 29605

  • Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Greenville Health System Cancer Institute-Eastside

    Greenville, South Carolina, 29615

  • Greenville Health System Cancer Institute-Greer

    Greer, South Carolina, 29650

  • William Beaumont Hospital-Grosse Point

    Grosse Pointe, Michigan, 48230

  • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center

    Grosse Pointe Woods, Michigan, 48236

  • Lymphoma Clinic of Michigan

    Grosse Pointe Woods, Michigan, 48236

  • Michigan Breast Specialists-Grosse Pointe Woods

    Grosse Pointe Woods, Michigan, 48236

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Cancer and Blood Specialists-Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada - Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada-Horizon Ridge

    Henderson, Nevada, 89052

  • Las Vegas Cancer Center-Henderson

    Henderson, Nevada, 89052

  • Nevada Cancer Specialists-Saint Rose

    Henderson, Nevada, 89052

  • 21st Century Oncology-Henderson

    Henderson, Nevada, 89074

  • Comprehensive Cancer Centers of Nevada-Southeast Henderson

    Henderson, Nevada, 89074

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • New Hampshire Oncology Hematology PA-Hooksett

    Hooksett, New Hampshire, 03106

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Centerpoint Medical Center LLC

    Independence, Missouri, 64057

  • Community Cancer Center East

    Indianapolis, Indiana, 46219

  • Community Cancer Center South

    Indianapolis, Indiana, 46227

  • Community Cancer Center North

    Indianapolis, Indiana, 46256

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Allegiance Health

    Jackson, Michigan, 49201

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Onslow Memorial Hospital

    Jacksonville, North Carolina, 28546

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

  • Essentia Health - Jamestown Clinic

    Jamestown, North Dakota, 58401

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • Kalispell Regional Medical Center

    Kalispell, Montana, 59901

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Research Medical Center

    Kansas City, Missouri, 64132

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • First Dayton Cancer Care

    Kettering, Ohio, 45420

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Community Howard Regional Health

    Kokomo, Indiana, 46904

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Desert West Surgery

    Las Vegas, Nevada, 89102

  • Nevada Cancer Specialists?Oakey

    Las Vegas, Nevada, 89102

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada, 89102

  • Cancer and Blood Specialists-Shadow

    Las Vegas, Nevada, 89106

  • Radiation Oncology Centers of Nevada Central

    Las Vegas, Nevada, 89106

  • 21st Century Oncology

    Las Vegas, Nevada, 89109

  • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway

    Las Vegas, Nevada, 89109

  • HealthCare Partners Medical Group Oncology/Hematology-San Martin

    Las Vegas, Nevada, 89113

  • Radiation Oncology Centers of Nevada Southeast

    Las Vegas, Nevada, 89119

  • Cancer Therapy and Integrative Medicine

    Las Vegas, Nevada, 89121

  • 21st Century Oncology-Vegas Tenaya

    Las Vegas, Nevada, 89128

  • Ann M Wierman MD LTD

    Las Vegas, Nevada, 89128

  • Cancer and Blood Specialists-Tenaya

    Las Vegas, Nevada, 89128

  • Comprehensive Cancer Centers of Nevada - Northwest

    Las Vegas, Nevada, 89128

  • HealthCare Partners Medical Group Oncology/Hematology-Tenaya

    Las Vegas, Nevada, 89128

  • Nevada Cancer Specialists-Tenaya

    Las Vegas, Nevada, 89128

  • Comprehensive Cancer Centers of Nevada-Summerlin

    Las Vegas, Nevada, 89144

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

  • Las Vegas Cancer Center-Medical Center

    Las Vegas, Nevada, 89148-2405

  • 21st Century Oncology-Fort Apache

    Las Vegas, Nevada, 89148

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

  • Nevada Cancer Specialists-Fort Apache

    Las Vegas, Nevada, 89148

  • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills

    Las Vegas, Nevada, 89149

  • Comprehensive Cancer Centers of Nevada - Central Valley

    Las Vegas, Nevada, 89169

  • University Cancer Center

    Las Vegas, Nevada, 89169

  • Saint Luke's East - Lee's Summit

    Lee's Summit, Missouri, 64086

  • Kansas Institute of Medicine Cancer and Blood Center

    Lenexa, Kansas, 66219

  • Minimally Invasive Surgery Hospital

    Lenexa, Kansas, 66219

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Hope Cancer Clinic

    Livonia, Michigan, 48154

  • Saint Mary Mercy Hospital

    Livonia, Michigan, 48154

  • PeaceHealth Saint John Medical Center

    Longview, Washington, 98632

  • Great Lakes Cancer Management Specialists-Macomb Medical Campus

    Macomb, Michigan, 48044

  • Michigan Breast Specialists-Macomb Township

    Macomb, Michigan, 48044

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Saint Mary's Oncology/Hematology Associates of Marlette

    Marlette, Michigan, 48453

  • WVUH-Berkely Medical Center

    Martinsburg, West Virginia, 25401

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Cone Heath Cancer Center at Mebane

    Mebane, North Carolina, 27302

  • Idaho Urologic Institute-Meridian

    Meridian, Idaho, 83642

  • Saint Luke's Mountain States Tumor Institute - Meridian

    Meridian, Idaho, 83642

  • Dayton Physicians LLC-Signal Point

    Middletown, Ohio, 45042

  • Memorial Regional Cancer Center Day Road

    Mishawaka, Indiana, 46545

  • Community Medical Hospital

    Missoula, Montana, 59804

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Good Samaritan Regional Health Center

    Mount Vernon, Illinois, 62864

  • Lowcountry Hematology Oncology PA-Mount Pleasant

    Mt. Pleasant, South Carolina, 29464

  • Saint Alphonsus Medical Center-Nampa

    Nampa, Idaho, 83686

  • Saint Luke's Mountain States Tumor Institute - Nampa

    Nampa, Idaho, 83686

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Regional Hematology and Oncology PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Chancellor Center for Oncology

    Newburgh, Indiana, 47630

  • Ascension Providence Hospitals - Novi

    Novi, Michigan, 48374

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • Saint Alphonsus Medical Center-Ontario

    Ontario, Oregon, 97914

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • Menorah Medical Center

    Overland Park, Kansas, 66209

  • Saint Luke's South Hospital

    Overland Park, Kansas, 66213

  • Hope Cancer Care of Nevada-Pahrump

    Pahrump, Nevada, 89048

  • Essentia Health - Park Rapids

    Park Rapids, Minnesota, 56470

  • Camden Clark Medical Center

    Parkersburg, West Virginia, 26101

  • 21st Century Oncology-Pontiac

    Pontiac, Michigan, 48341

  • Hope Cancer Center

    Pontiac, Michigan, 48341

  • Newland Medical Associates-Pontiac

    Pontiac, Michigan, 48341

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Huron Medical Center PC

    Port Huron, Michigan, 48060

  • Lake Huron Medical Center

    Port Huron, Michigan, 48060

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Kootenai Cancer Center

    Post Falls, Idaho, 83854

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Annie Penn Memorial Hospital

    Reidsville, North Carolina, 27320

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Saint Mary's Regional Medical Center

    Reno, Nevada, 89503

  • Radiation Oncology Associates

    Reno, Nevada, 89509

  • Reid Health

    Richmond, Indiana, 47374

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Great Lakes Cancer Management Specialists-Rochester Hills

    Rochester Hills, Michigan, 48309

  • Delbert Day Cancer Institute at PCRMC

    Rolla, Missouri, 65401

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Michigan Cancer Specialists

    Roseville, Michigan, 48066

  • Oakland Colon and Rectal Association

    Royal Oak, Michigan, 48067

  • Cancer Care Associates PC

    Royal Oak, Michigan, 48073

  • Comprehensive Medical Center PLLC

    Royal Oak, Michigan, 48073

  • Hematology Oncology Consultants PC

    Royal Oak, Michigan, 48073

  • Oakland Medical Group

    Royal Oak, Michigan, 48073

  • William Beaumont Hospital-Royal Oak

    Royal Oak, Michigan, 48073

  • Saint Mary's of Michigan

    Saginaw, Michigan, 48601

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64507

  • Kootenai Cancer Clinic

    Sandpoint, Idaho, 83864

  • Essentia Health Sandstone

    Sandstone, Minnesota, 55072

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Summit Cancer Care-Memorial

    Savannah, Georgia, 31404

  • Low Country Cancer Care Associates PC

    Savannah, Georgia, 31405

  • Summit Cancer Care-Candler

    Savannah, Georgia, 31405

  • Nanticoke Memorial Hospital

    Seaford, Delaware, 19973

  • Pacific Gynecology Specialists

    Seattle, Washington, 98104

  • Swedish Medical Center-Ballard Campus

    Seattle, Washington, 98107

  • Kaiser Permanente Washington

    Seattle, Washington, 98112

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122-4307

  • Swedish Medical Center-Cherry Hill

    Seattle, Washington, 98122-5711

  • Greenville Health System Cancer Institute-Seneca

    Seneca, South Carolina, 29672

  • Providence Regional Cancer System-Shelton

    Shelton, Washington, 98584

  • Welch Cancer Center

    Sheridan, Wyoming, 82801

  • Dayton Physicians LLC-Wilson

    Sidney, Ohio, 45365

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Ascension Providence Hospitals - Southfield

    Southfield, Michigan, 48075

  • Greenville Health System Cancer Institute-Spartanburg

    Spartanburg, South Carolina, 29307

  • Rockwood Cancer Treatment Center-DHEC-Downtown

    Spokane, Washington, 99204

  • Rockwood North Cancer Treatment Center

    Spokane, Washington, 99218

  • Rockwood Clinic Cancer Treatment Center-Valley

    Spokane Valley, Washington, 99216

  • Mercy Medical Center

    Springfield, Massachusetts, 01104

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Springfield Regional Cancer Center

    Springfield, Ohio, 45504

  • Springfield Regional Medical Center

    Springfield, Ohio, 45505

  • Saint Louis Cancer and Breast Institute-South City

    St Louis, Missouri, 63109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Bhadresh Nayak MD PC-Sterling Heights

    Sterling Heights, Michigan, 48312

  • Premier Hematology Oncology Care

    Sterling Heights, Michigan, 48312

Other trials in United States

Canada9 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • CHUM - Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 3E4

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa Hospital and Cancer Center-General Campus

    Ottawa, Ontario, K1H 8L6

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec, J1H 5N4

  • Odette Cancer Centre- Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: Randomized Phase II Study: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases

This randomized phase II study aims to investigate whether the addition of bevacizumab to standard corticosteroid therapy results in greater improvement in symptoms and less treatment-induced symptoms compared with standard corticosteroid therapy for patients with symptomatic brain radionecrosis following radiosurgery. It is hypothesized that the addition of bevacizumab to standard care corticosteroids will reduce treatment-induced toxicities and improve neurologic impairments in patients with brain radionecrosis following radiosurgery for brain metastases.

Read the detailed description

This is a randomized double-blinded phase II study of corticosteroids with bevacizumab vs. corticosteroids with placebo for brain radionecrosis following radiosurgery for brain metastases. This is a two-arm clinical trial with parallel group design for longitudinal quality of life endpoint. Patients will be stratified according to age (≤ 65 years vs. > 65 years), pathological confirmation of necrosis (yes vs. no), MDASI-BT mean global score (symptom + interference scores) ( < 4.0 vs. > 4.0) and prior whole brain radiotherapy (yes vs. no). The primary and secondary objectives are detailed below.

Primary Objective:

To investigate whether the addition of bevacizumab to standard corticosteroid therapy results in greater improvement in symptoms (clinical and patient-reported symptom improvement associated with radionecrosis and less radionecrosis treatment-induced symptoms) compared with standard corticosteroid therapy.

Secondary Objectives:

  1. To evaluate the toxicity profile associated with bevacizumab and corticosteroid therapy.
  2. To compare self-reported health related quality of life (HRQOL) using LASA, Dexamethasone Symptoms Questionnaire-Chronic (DSQ-C), and MDASI-BT symptom and interference score between treatment arms.
  3. To compare intracranial progression-free survival and time to maximum radiographic response between treatment arms.
  4. To compare the dose and duration of corticosteroids required between treatment arms and correlate steroid requirement with DSQ-C and MDASI-BT scores.

Patient event monitoring will occur every 2 months after treatment up to 6 months. Then event monitoring will occur up to one year.

Being tested
bevacizumab, corticosteroids, placebo
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02490878
Study groupRoleWhat they receive
bevacizumab + corticosteroidsExperimentalThe patient will receive bevacizumab 10 mg/kg IV given on days 1 and 15 of a 28 day cycle for 4 cycles. Once the patient has started the study treatment, the dose of corticosteroids will be tapered every 5 days (e.g., dexamethasone 2 mg or prednisone 15 mg per taper), as tolerated, under the management of the treating MD. If patients deteriorate while tapering, dexamethasone will be increased up to a maximum of 16 mg per day, as per treating MD, to manage symptoms. Patients who meet the criteria for clinical progression will be treated as per treating MD.
Receives: Drug: bevacizumab; Drug: corticosteroids
placebo + corticosteroidsExperimentalThe patient will receive placebo 0.9% NaCl volume equal to bevacizumab volume added to 100 mL bag of 0.9% NaCl delivered IV given on days 1 and 15 of a 28-day cycle for 4 cycles. Once the patient has started the study treatment, the dose of corticosteroids will be tapered every 5 days (e.g., dexamethasone 2 mg or prednisone 15 mg per taper), as tolerated, under the management of the treating MD. If patients deteriorate while tapering, dexamethasone will be increased up to a maximum of 16 mg per day, as per treating MD, to manage symptoms. Patients who meet the criteria for clinical progression will be allowed to receive bevacizumab according to the protocol.
Receives: Drug: corticosteroids; Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score

    The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Symptom Severity) is the average of the subscale items with 0 being "not present" and 10 being "as bad as you can imagine.", given that a specified minimum numbers of items were completed. A negative change in score from baseline to given time point indicates a worsening score.

    Measured: Baseline, 2, 4, 6 and 8 weeks

Secondary outcomes (7)

  1. Toxicity (CTCAE Version 4.0)

    Toxicity associated with bevacizumab and corticosteroids in patients with radionecrosis using CTCAE Version 4.0. The number of patients reporting a grade 3 or higher, 4 or higher, or 5 at least possibly related to treatment are included in this table.

    Measured: Up to 1.5 years post-treatment

  2. Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA)

    The Linear Analogue Scale used is a 5-question survey. Patients are asked to score the following questions on a 1(as bad as it can be) -10 (as good as it can be) scale: 1) your overall quality of life, 2) your overall (intellectual) well being, 3) your overall physical well being, 4) your overall emotional well being, and 5) your overall spiritual well being. The change in score was computed from baseline to 1.5 years post-treatment. A negative difference is thought of as a worsening score from baseline.

    Measured: Up to 1.5 years post-treatment

  3. Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C)

    The DSQ-C was developed for use in the brain tumor patient population. It consists of 18 questions rated on a 4-point scale (1 to 4, with 4 indicating a worse symptom) to indicate the presence and severity of symptoms. For each patient, the sum across all 18 questions were computed(18-72, with 18 being a score of 1 for each of the 18 questions and 72 being a score of 4 for each of the questions, refering to the previous sentence, a score of 18(a score of 1, 18 times) indicates the best possible score. A score of 72(a score of 4, 18 times) indicates the worst possible. The mean for total score across each week (weeks 2, 4, 6, 8) is reported.

    Measured: Baseline and weeks 2, 4, 6, 8 of treatment

  4. Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score.

    The MDASI-BT was developed and validated for use in the brain tumor patient population, including those with brain metastases and typically requires less than 4 minutes to complete. It consists of 23 symptoms rated on a 0 to 10 numerical rating scale (NRS) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." MDASI-BT Symptom Scoring: A global symptom score for the MDASI symptom severity scale is obtained by taking the average of the 23 items together. This puts the score on a 0-10 scalenumerical rating scale (NRS) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." The mean global symptom at baseline and at weeks 2, 4, 6, 8 were used in this analysis.

    Measured: Up to 1.5 years post-treatment

  5. Progression Free Survival

    Progression free survival is defined as the time from start of treatment to the earliest of the date patient stops placebo or bevacizumab for either alternative therapy or crossover to bevacizumab (if initially on placebo). Result will be summarized by Kaplan-Meier method.

    Measured: Up to 16 weeks

  6. Time to Maximum Radiographic Response

    Time from start of treatment to maximum radiographic response

    Measured: Up to 16 weeks

  7. Time to Stopping Corticosteroids

    Time to stopping corticosteroids is defined as the time from start of protocol treatment to the last day corticosteroids were given. Time to stopping corticosteroid will be summarized by Kaplan-Meier curve with log-rank tests conducted to investigate differences between treatment arms.

    Measured: Up to 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jul 2015 (estimated)
  2. Study startApr 2016
  3. Primary completion1 Feb 2019
  4. Study completion15 Dec 2022

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02490878
Sponsor's protocol ID
A221208
Other IDs
NCI-2015-01348
Status last verified
Feb 2023
First submitted
2 Jul 2015
Last updated
23 Mar 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab and corticosteroids in people with Radionecrosis and Brain Metastases, run by Alliance for Clinical Trials in Oncology at 341 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 341 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score (time frame: Baseline, 2, 4, 6 and 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02490878.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2023.

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