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

Brain Metastases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02490878
• Other study ID #: A221208
• Secondary ID: NCI-2015-01348
• Status: Terminated
• Phase: Phase 2
• Start date: April 2016
• Est. completion date: December 15, 2022

Study information

• Verified date: February 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Other known NCT identifiers

• NCT02531659

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: December 15, 2022
• Est. primary completion date: February 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis
• Radionecrosis

Intervention

Drug:
• bevacizumab
IV
• corticosteroids
IV

Other:
• placebo
IV

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	PCR Oncology	Arroyo Grande	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	Ashland Memorial Medical Center	Ashland	Wisconsin
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	University Cancer and Blood Center LLC	Athens	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	United Hospital Center	Bridgeport	West Virginia
United States	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	IHA Hematology Oncology Consultants-Canton	Canton	Michigan
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Caro Cancer Center	Caro	Michigan
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Bon Secours Saint Francis Hospital	Charleston	South Carolina
United States	Charleston Hematology Oncology Associates PA-Saint Francis	Charleston	South Carolina
United States	Charleston Hematology Oncology Associates-Roper	Charleston	South Carolina
United States	Lowcountry Hematology Oncology PA-North Charleston	Charleston	South Carolina
United States	Lowcountry Hematology Oncology PA-West Ashley	Charleston	South Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Greenville Health System Cancer Institute-Laurens	Clinton	South Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Carle on Vermilion	Danville	Illinois
United States	Dayton Physicians LLC-Samaritan North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Halifax Health Medical Center-Centers for Oncology	Daytona Beach	Florida
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Greenville Health System Cancer Institute-Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Swedish Medical Center-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Memorial Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	William Beaumont Hospital-Grosse Point	Grosse Pointe	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Lymphoma Clinic of Michigan	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Saint Peter's Community Hospital	Helena	Montana
United States	21st Century Oncology-Henderson	Henderson	Nevada
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Nevada Cancer Specialists-Saint Rose	Henderson	Nevada
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire
United States	M D Anderson Cancer Center	Houston	Texas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Community Cancer Center South	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Community Howard Regional Health	Kokomo	Indiana
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Sparrow Hospital	Lansing	Michigan
United States	21st Century Oncology	Las Vegas	Nevada
United States	21st Century Oncology-Fort Apache	Las Vegas	Nevada
United States	21st Century Oncology-Vegas Tenaya	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Specialists-Fort Apache	Las Vegas	Nevada
United States	Nevada Cancer Specialists-Tenaya	Las Vegas	Nevada
United States	Nevada Cancer Specialists?Oakey	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	Dayton Physicians LLC-Signal Point	Middletown	Ohio
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Community Medical Hospital	Missoula	Montana
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Lowcountry Hematology Oncology PA-Mount Pleasant	Mount Pleasant	South Carolina
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Regional Hematology and Oncology PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Chancellor Center for Oncology	Newburgh	Indiana
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Reid Health	Richmond	Indiana
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Michigan Cancer Specialists	Roseville	Michigan
United States	Cancer Care Associates PC	Royal Oak	Michigan
United States	Comprehensive Medical Center PLLC	Royal Oak	Michigan
United States	Hematology Oncology Consultants PC	Royal Oak	Michigan
United States	Oakland Colon and Rectal Association	Royal Oak	Michigan
United States	Oakland Medical Group	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Low Country Cancer Care Associates PC	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Summit Cancer Care-Candler	Savannah	Georgia
United States	Summit Cancer Care-Memorial	Savannah	Georgia
United States	Nanticoke Memorial Hospital	Seaford	Delaware
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Dayton Physicians LLC-Wilson	Sidney	Ohio
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington
United States	Rockwood North Cancer Treatment Center	Spokane	Washington
United States	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Massachusetts
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Mitchell Folbe MD PC	Sterling Heights	Michigan
United States	Premier Hematology Oncology Care	Sterling Heights	Michigan
United States	Overlook Hospital	Summit	New Jersey
United States	Moffitt Cancer Center	Tampa	Florida
United States	Saint Joseph Health System-Tawas City	Tawas City	Michigan
United States	Claudia BR Herke MD PC	Troy	Michigan
United States	Dayton Physicians LLC-Upper Valley	Troy	Ohio
United States	Hematology Oncology Consultants PC-Troy	Troy	Michigan
United States	Michigan Institute of Urology-Town Center	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Bhadresh Nayak MD PC-Warren	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Mercy Hospital Washington	Washington	Missouri
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	Genentech, Inc., National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, 2, 4, 6 and 8 weeks
Secondary	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.	Up to 1.5 years post-treatment
Secondary	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.	Up to 1.5 years post-treatment
Secondary	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.	Baseline and weeks 2, 4, 6, 8 of treatment
Secondary	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.	Up to 1.5 years post-treatment
Secondary	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.	Up to 16 weeks
Secondary	Time to Maximum Radiographic Response	Time from start of treatment to maximum radiographic response	Up to 16 weeks
Secondary	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.	Up to 16 weeks