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

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02490878
• Collaborator: National Cancer Institute (NCI) (NIH), Genentech, Inc. (Industry)
• Enrollment: 19
• Locations: 341
• Arms: 2
• Actual Duration (Months): 48.8
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Radionecrosis; Brain Metastases	Drug: bevacizumab; Drug: corticosteroids; Other: placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Randomized Phase II Study: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Feb 1, 2019
• Actual Study Completion Date: Apr 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bevacizumab + corticosteroids The 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.	Drug: bevacizumab; IV; Drug: corticosteroids; IV
Experimental: placebo + corticosteroids The 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.	Drug: corticosteroids; IV; Other: placebo; IV

Outcome Measures

Primary Outcome Measures

1. Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score [Baseline, 2, 4, 6 and 8 weeks]

   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.

Secondary Outcome Measures

1. Toxicity (CTCAE Version 4.0) [Up to 1.5 years post-treatment]

   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.

2. Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) [Up to 1.5 years post-treatment]

   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.

3. Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) [Baseline and weeks 2, 4, 6, 8 of treatment]

   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.

4. Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. [Up to 1.5 years post-treatment]

   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.

5. Progression Free Survival [Up to 16 weeks]

   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.

6. Time to Maximum Radiographic Response [Up to 16 weeks]

   Time from start of treatment to maximum radiographic response

7. Time to Stopping Corticosteroids [Up to 16 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

1. 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.

2. Age ≥ 18 years

3. Karnofsky Performance Status ≥ 60%

4. 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

1. 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.

1. 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.

2. 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.

1. 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.

1. No history of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within past 12 months.

2. No central lung metastases with excessive active bleeding.

3. 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.

1. No history of serious non-healing wound, ulcer, or bone fractures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
2	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
3	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
4	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
5	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
6	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
7	Katmai Oncology Group	Anchorage	Alaska	United States	99508
8	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
9	PCR Oncology	Arroyo Grande	California	United States	93420
10	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
11	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
12	Beebe Medical Center	Lewes	Delaware	United States	19958
13	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
14	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
15	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
16	Regional Hematology and Oncology PA	Newark	Delaware	United States	19713
17	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
18	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
19	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
20	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
21	Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
22	Halifax Health Medical Center-Centers for Oncology	Daytona Beach	Florida	United States	32114
23	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
24	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
25	Moffitt Cancer Center	Tampa	Florida	United States	33612
26	University Cancer and Blood Center LLC	Athens	Georgia	United States	30607
27	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
28	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
29	Summit Cancer Care-Memorial	Savannah	Georgia	United States	31404
30	Low Country Cancer Care Associates PC	Savannah	Georgia	United States	31405
31	Summit Cancer Care-Candler	Savannah	Georgia	United States	31405
32	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
33	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
34	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
35	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
36	Walter Knox Memorial Hospital	Emmett	Idaho	United States	83617
37	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho	United States	83619
38	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
39	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
40	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
41	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho	United States	83686
42	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
43	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
44	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho	United States	83301
45	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
46	Rush University Medical Center	Chicago	Illinois	United States	60612
47	University of Illinois	Chicago	Illinois	United States	60612
48	Carle on Vermilion	Danville	Illinois	United States	61832
49	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
50	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
51	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
52	Carle Cancer Center	Urbana	Illinois	United States	61801
53	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
54	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
55	Deaconess Clinic Downtown	Evansville	Indiana	United States	47713
56	Community Cancer Center East	Indianapolis	Indiana	United States	46219
57	Community Cancer Center South	Indianapolis	Indiana	United States	46227
58	Community Cancer Center North	Indianapolis	Indiana	United States	46256
59	Community Howard Regional Health	Kokomo	Indiana	United States	46904
60	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
61	Chancellor Center for Oncology	Newburgh	Indiana	United States	47630
62	Reid Health	Richmond	Indiana	United States	47374
63	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
64	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
65	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
66	Broadlawns Medical Center	Des Moines	Iowa	United States	50314
67	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
68	Trinity Regional Medical Center	Fort Dodge	Iowa	United States	50501
69	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
70	Central Care Cancer Center - Garden City	Garden City	Kansas	United States	67846
71	Central Care Cancer Center - Great Bend	Great Bend	Kansas	United States	67530
72	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas	United States	66219
73	Minimally Invasive Surgery Hospital	Lenexa	Kansas	United States	66219
74	Menorah Medical Center	Overland Park	Kansas	United States	66209
75	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
76	Mercy Medical Center	Springfield	Massachusetts	United States	01104
77	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
78	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
79	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan	United States	48114
80	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
81	IHA Hematology Oncology Consultants-Canton	Canton	Michigan	United States	48188
82	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
83	Caro Cancer Center	Caro	Michigan	United States	48723
84	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan	United States	48118
85	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
86	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan	United States	48346
87	Newland Medical Associates-Clarkston	Clarkston	Michigan	United States	48346
88	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
89	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
90	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan	United States	48054
91	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan	United States	48336
92	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan	United States	48503
93	Genesee Hematology Oncology PC	Flint	Michigan	United States	48503
94	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
95	Hurley Medical Center	Flint	Michigan	United States	48503
96	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan	United States	48236
97	Lymphoma Clinic of Michigan	Grosse Pointe Woods	Michigan	United States	48236
98	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan	United States	48236
99	William Beaumont Hospital-Grosse Point	Grosse Pointe	Michigan	United States	48230
100	Allegiance Health	Jackson	Michigan	United States	49201
101	Sparrow Hospital	Lansing	Michigan	United States	48912
102	Hope Cancer Clinic	Livonia	Michigan	United States	48154
103	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
104	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan	United States	48044
105	Michigan Breast Specialists-Macomb Township	Macomb	Michigan	United States	48044
106	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan	United States	48453
107	Ascension Providence Hospitals - Novi	Novi	Michigan	United States	48374
108	21st Century Oncology-Pontiac	Pontiac	Michigan	United States	48341
109	Hope Cancer Center	Pontiac	Michigan	United States	48341
110	Newland Medical Associates-Pontiac	Pontiac	Michigan	United States	48341
111	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
112	Huron Medical Center PC	Port Huron	Michigan	United States	48060
113	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
114	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan	United States	48309
115	Michigan Cancer Specialists	Roseville	Michigan	United States	48066
116	Oakland Colon and Rectal Association	Royal Oak	Michigan	United States	48067
117	Cancer Care Associates PC	Royal Oak	Michigan	United States	48073
118	Comprehensive Medical Center PLLC	Royal Oak	Michigan	United States	48073
119	Hematology Oncology Consultants PC	Royal Oak	Michigan	United States	48073
120	Oakland Medical Group	Royal Oak	Michigan	United States	48073
121	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
122	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
123	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan	United States	48604
124	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
125	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan	United States	48312
126	Premier Hematology Oncology Care	Sterling Heights	Michigan	United States	48312
127	Mitchell Folbe MD PC	Sterling Heights	Michigan	United States	48314
128	Saint Joseph Health System-Tawas City	Tawas City	Michigan	United States	48764
129	Michigan Institute of Urology-Town Center	Troy	Michigan	United States	48084
130	Claudia BR Herke MD PC	Troy	Michigan	United States	48085
131	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
132	Hematology Oncology Consultants PC-Troy	Troy	Michigan	United States	48098
133	Advanced Breast Care Center PLLC	Warren	Michigan	United States	48088
134	Bhadresh Nayak MD PC-Warren	Warren	Michigan	United States	48093
135	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan	United States	48093
136	Macomb Hematology Oncology PC	Warren	Michigan	United States	48093
137	Michigan Breast Specialists-Warren	Warren	Michigan	United States	48093
138	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
139	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan	United States	48661
140	Huron Gastroenterology PC	Ypsilanti	Michigan	United States	48106
141	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan	United States	48197
142	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
143	Essentia Health - Deer River Clinic	Deer River	Minnesota	United States	56636
144	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota	United States	56501
145	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
146	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
147	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
148	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
149	Essentia Health - Fosston	Fosston	Minnesota	United States	56542
150	Essentia Health Hibbing Clinic	Hibbing	Minnesota	United States	55746
151	Essentia Health - Park Rapids	Park Rapids	Minnesota	United States	56470
152	Mayo Clinic	Rochester	Minnesota	United States	55905
153	Essentia Health Sandstone	Sandstone	Minnesota	United States	55072
154	Essentia Health Virginia Clinic	Virginia	Minnesota	United States	55792
155	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri	United States	63011
156	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
157	Cox Cancer Center Branson	Branson	Missouri	United States	65616
158	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
159	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
160	Freeman Health System	Joplin	Missouri	United States	64804
161	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
162	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
163	Research Medical Center	Kansas City	Missouri	United States	64132
164	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
165	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
166	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
167	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64507
168	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
169	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
170	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri	United States	63376
171	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
172	CoxHealth South Hospital	Springfield	Missouri	United States	65807
173	Mercy Hospital Washington	Washington	Missouri	United States	63090
174	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
175	Billings Clinic Cancer Center	Billings	Montana	United States	59101
176	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
177	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
178	Great Falls Clinic	Great Falls	Montana	United States	59405
179	Saint Peter's Community Hospital	Helena	Montana	United States	59601
180	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
181	Community Medical Hospital	Missoula	Montana	United States	59804
182	Carson Tahoe Regional Medical Center	Carson City	Nevada	United States	89703
183	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
184	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
185	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada	United States	89052
186	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
187	Nevada Cancer Specialists-Saint Rose	Henderson	Nevada	United States	89052
188	21st Century Oncology-Henderson	Henderson	Nevada	United States	89074
189	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
190	Desert West Surgery	Las Vegas	Nevada	United States	89102
191	Nevada Cancer Specialists?Oakey	Las Vegas	Nevada	United States	89102
192	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
193	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
194	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
195	21st Century Oncology	Las Vegas	Nevada	United States	89109
196	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
197	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
198	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
199	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
200	21st Century Oncology-Vegas Tenaya	Las Vegas	Nevada	United States	89128
201	Ann M Wierman MD LTD	Las Vegas	Nevada	United States	89128
202	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
203	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
204	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
205	Nevada Cancer Specialists-Tenaya	Las Vegas	Nevada	United States	89128
206	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
207	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
208	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
209	21st Century Oncology-Fort Apache	Las Vegas	Nevada	United States	89148
210	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
211	Nevada Cancer Specialists-Fort Apache	Las Vegas	Nevada	United States	89148
212	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
213	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
214	University Cancer Center	Las Vegas	Nevada	United States	89169
215	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada	United States	89048
216	Renown Regional Medical Center	Reno	Nevada	United States	89502
217	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
218	Radiation Oncology Associates	Reno	Nevada	United States	89509
219	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire	United States	03301
220	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire	United States	03106
221	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
222	Overlook Hospital	Summit	New Jersey	United States	07902
223	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
224	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
225	University of Rochester	Rochester	New York	United States	14642
226	Randolph Hospital	Asheboro	North Carolina	United States	27203
227	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
228	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
229	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
230	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
231	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
232	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
233	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
234	East Carolina University	Greenville	North Carolina	United States	27834
235	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
236	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
237	Cone Heath Cancer Center at Mebane	Mebane	North Carolina	United States	27302
238	Annie Penn Memorial Hospital	Reidsville	North Carolina	United States	27320
239	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina	United States	27893
240	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
241	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
242	Essentia Health - Jamestown Clinic	Jamestown	North Dakota	United States	58401
243	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
244	Indu and Raj Soin Medical Center	Beavercreek	Ohio	United States	45431
245	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
246	Miami Valley Hospital South	Centerville	Ohio	United States	45459
247	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
248	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
249	Miami Valley Hospital	Dayton	Ohio	United States	45409
250	Dayton Physicians LLC-Samaritan North	Dayton	Ohio	United States	45415
251	Miami Valley Hospital North	Dayton	Ohio	United States	45415
252	Armes Family Cancer Center	Findlay	Ohio	United States	45840
253	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
254	Orion Cancer Care	Findlay	Ohio	United States	45840
255	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
256	Dayton Physicians LLC-Atrium	Franklin	Ohio	United States	45005
257	Dayton Physicians LLC-Wayne	Greenville	Ohio	United States	45331
258	Wayne Hospital	Greenville	Ohio	United States	45331
259	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
260	First Dayton Cancer Care	Kettering	Ohio	United States	45420
261	Kettering Medical Center	Kettering	Ohio	United States	45429
262	Dayton Physicians LLC-Signal Point	Middletown	Ohio	United States	45042
263	Dayton Physicians LLC-Wilson	Sidney	Ohio	United States	45365
264	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
265	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
266	Dayton Physicians LLC-Upper Valley	Troy	Ohio	United States	45373
267	Upper Valley Medical Center	Troy	Ohio	United States	45373
268	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
269	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon	United States	97814
270	Saint Charles Health System	Bend	Oregon	United States	97701
271	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
272	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon	United States	97015
273	Bay Area Hospital	Coos Bay	Oregon	United States	97420
274	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
275	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon	United States	97914
276	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
277	Providence Portland Medical Center	Portland	Oregon	United States	97213
278	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
279	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
280	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
281	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
282	Roper Hospital	Charleston	South Carolina	United States	29401
283	Charleston Hematology Oncology Associates-Roper	Charleston	South Carolina	United States	29403
284	Lowcountry Hematology Oncology PA-North Charleston	Charleston	South Carolina	United States	29406
285	Bon Secours Saint Francis Hospital	Charleston	South Carolina	United States	29414
286	Charleston Hematology Oncology Associates PA-Saint Francis	Charleston	South Carolina	United States	29414
287	Lowcountry Hematology Oncology PA-West Ashley	Charleston	South Carolina	United States	29414
288	Greenville Health System Cancer Institute-Laurens	Clinton	South Carolina	United States	29325
289	Greenville Health System Cancer Institute-Easley	Easley	South Carolina	United States	29640
290	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina	United States	29605
291	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
292	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
293	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina	United States	29615
294	Greenville Health System Cancer Institute-Greer	Greer	South Carolina	United States	29650
295	Lowcountry Hematology Oncology PA-Mount Pleasant	Mount Pleasant	South Carolina	United States	29464
296	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina	United States	29672
297	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
298	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee	United States	37067
299	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee	United States	37204
300	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
301	M D Anderson Cancer Center	Houston	Texas	United States	77030
302	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
303	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
304	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
305	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
306	Swedish Medical Center-Edmonds	Edmonds	Washington	United States	98026
307	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
308	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
309	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
310	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
311	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
312	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
313	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
314	Kaiser Permanente Washington	Seattle	Washington	United States	98112
315	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
316	Swedish Medical Center-Cherry Hill	Seattle	Washington	United States	98122-5711
317	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
318	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington	United States	99216
319	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington	United States	99204
320	Rockwood North Cancer Treatment Center	Spokane	Washington	United States	99218
321	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
322	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
323	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
324	United Hospital Center	Bridgeport	West Virginia	United States	26330
325	WVUH-Berkely Medical Center	Martinsburg	West Virginia	United States	25401
326	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
327	Camden Clark Medical Center	Parkersburg	West Virginia	United States	26101
328	Ashland Memorial Medical Center	Ashland	Wisconsin	United States	54806
329	Duluth Clinic Ashland	Ashland	Wisconsin	United States	54806
330	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
331	Billings Clinic-Cody	Cody	Wyoming	United States	82414
332	Welch Cancer Center	Sheridan	Wyoming	United States	82801
333	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
334	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
335	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario	Canada	K1H 8L6
336	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
337	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
338	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
339	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3E4
340	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
341	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4

Sponsors and Collaborators

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

Investigators

• Study Chair: Caroline Chung, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Nov 29, 2018

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT02490878
• Other Study ID Numbers: A221208; NCI-2015-01348; NCT02531659
• First Posted: Jul 7, 2015
• Last Update Posted: Aug 6, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Neoplasm Metastasis; Brain Neoplasms; Bevacizumab

Study Results

Participant Flow

Pre-assignment Detail	40 patients underwent pre-screening. Only 19 underwent randomization.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Period Title: Overall Study
STARTED	10	9
Eligible Participants	10	8
COMPLETED	10	6
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo	Total
Arm/Group Description	The 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.	The 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.	Total of all reporting groups
Overall Participants	10	6	16
Age, Customized (Count of Participants)
<= 65 years	7 70%	5 83.3%	12 75%
> 65 years	3 30%	1 16.7%	4 25%
Sex: Female, Male (Count of Participants)
Female	6 60%	4 66.7%	10 62.5%
Male	4 40%	2 33.3%	6 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 20%	0 0%	2 12.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 10%	0 0%	1 6.3%
White	7 70%	5 83.3%	12 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 16.7%	1 6.3%
Prior whole brain radiotherapy (Count of Participants)
Yes	5 50%	1 16.7%	6 37.5%
No	5 50%	5 83.3%	10 62.5%

Outcome Measures

1. Primary Outcome

Title	Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score
Description	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.
Time Frame	Baseline, 2, 4, 6 and 8 weeks

Outcome Measure Data

Analysis Population Description

All eligible patients that began protocol treatment and were assessed at baseline and at least one subsequent time within the first 8 weeks were included in this analysis.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	10	6
2 weeks	-0.8 (1.93)	0.1 (1.24)
4 weeks	-0.5 (2.17)	-2.0 (2.53)
6 weeks	-0.5 (2.33)	-2.3 (2.86)
8 weeks	-0.6 (2.13)	-3.9 (2.83)

2. Secondary Outcome

Title	Toxicity (CTCAE Version 4.0)
Description	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.
Time Frame	Up to 1.5 years post-treatment

Outcome Measure Data

Analysis Population Description

All patients that began treatment are included in this endpoint

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	10	8
Grade 3 or higher	2 20%	5 83.3%
Grade 4 or higher	0 0%	0 0%
Grade 5	0 0%	0 0%

3. Secondary Outcome

Title	Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA)
Description	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.
Time Frame	Up to 1.5 years post-treatment

Outcome Measure Data

Analysis Population Description

All patients that completed the LASA at baseline and at 1.5 years after treatment were included in this analysis.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	8	5
LASA Overall Quality of Life	-1.0 (3.07)	0.0 (2.55)
LASA Mental well being	-1.5 (3.12)	0.0 (1.73)
LASA Physical well being	-1.1 (3.4)	0.4 (1.14)
LASA Emotional well being	-1.0 (2.45)	1.8 (3.03)
LASA Spiritual well being	-1.1 (2.42)	0.8 (2.17)

4. Secondary Outcome

Title	Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C)
Description	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.
Time Frame	Baseline and weeks 2, 4, 6, 8 of treatment

Outcome Measure Data

Analysis Population Description

All patients that received protocol treatment and completed the survey at baseline were included in this analysis.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	10	7
Baseline	1.0 (0.15)	1.2 (0.33)
Week 2	1.0 (0.14)	1.2 (0.23)
Week 4	1.0 (0.14)	1.0 (0.14)
Week 6	1.0 (0.07)	1.0 (0.07)
Week 8	1.0 (0.15)	1.0 (0.16)

5. Secondary Outcome

Title	Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score.
Description	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.
Time Frame	Up to 1.5 years post-treatment

Outcome Measure Data

Analysis Population Description

All patients that began protocol treatment and completed the survey at study entry or within 8 weeks were included in this analysis

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	10	6
Baseline	4.0 (1.51)	5.3 (2.27)
Week 2	2.9 (2.39)	6.1 (0.88)
Week 4	3.9 (2.75)	4.8 (1.73)
Week 6	3.9 (2.21)	4.9 (3.29)
Week 8	4.0 (2.44)	4.3 (3.06)

6. Secondary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

All patients that registered were included in this analysis.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	10	9
Median (95% Confidence Interval) [days]	NA	NA

7. Secondary Outcome

Title	Time to Maximum Radiographic Response
Description	Time from start of treatment to maximum radiographic response
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

Due to early trial termination data was not collected and could not be analyzed.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	0	0

8. Secondary Outcome

Title	Time to Stopping Corticosteroids
Description	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.
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

All patients that registered for treatment were included in this analysis.

Arm/Group Title	Arm A: Bevacizumab	Arm B: Placebo
Arm/Group Description	The 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.	The 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.
Measure Participants	10	9
Median (95% Confidence Interval) [days]	113	102

Adverse Events

Time Frame	Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Arm/Group Title	Arm A: Bevacizumab		Arm B: Placebo
Arm/Group Description	The 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.		The 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.
All Cause Mortality
	Arm A: Bevacizumab		Arm B: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/8 (12.5%)
Serious Adverse Events
	Arm A: Bevacizumab		Arm B: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		6/8 (75%)
General disorders
Fever	1/10 (10%)	1	0/8 (0%)	0
Infections and infestations
Infections and infestations - Oth spec	0/10 (0%)	0	1/8 (12.5%)	2
Lung infection	0/10 (0%)	0	1/8 (12.5%)	1
Sepsis	0/10 (0%)	0	1/8 (12.5%)	1
Investigations
Alanine aminotransferase increased	0/10 (0%)	0	1/8 (12.5%)	1
CPK increased	0/10 (0%)	0	1/8 (12.5%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/10 (10%)	1	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/10 (10%)	1	0/8 (0%)	0
Muscle weakness lower limb	0/10 (0%)	0	2/8 (25%)	2
Nervous system disorders
Depressed level of consciousness	0/10 (0%)	0	1/8 (12.5%)	1
Dysgeusia	0/10 (0%)	0	1/8 (12.5%)	1
Dysphasia	0/10 (0%)	0	1/8 (12.5%)	1
Headache	0/10 (0%)	0	1/8 (12.5%)	1
Seizure	0/10 (0%)	0	2/8 (25%)	3
Psychiatric disorders
Confusion	1/10 (10%)	1	1/8 (12.5%)	1
Vascular disorders
Thromboembolic event	0/10 (0%)	0	1/8 (12.5%)	2
Other (Not Including Serious) Adverse Events
	Arm A: Bevacizumab		Arm B: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Anemia	0/10 (0%)	0	1/8 (12.5%)	6
Endocrine disorders
Cushingoid	1/10 (10%)	3	0/8 (0%)	0
Eye disorders
Blurred vision	1/10 (10%)	2	1/8 (12.5%)	1
Gastrointestinal disorders
Diarrhea	1/10 (10%)	1	0/8 (0%)	0
Dry mouth	1/10 (10%)	4	0/8 (0%)	0
Dysphagia	2/10 (20%)	4	0/8 (0%)	0
Gastrointestinal disorders - Oth spec	0/10 (0%)	0	1/8 (12.5%)	1
Nausea	1/10 (10%)	1	0/8 (0%)	0
Stomach pain	0/10 (0%)	0	1/8 (12.5%)	1
General disorders
Chills	1/10 (10%)	1	0/8 (0%)	0
Fatigue	4/10 (40%)	12	4/8 (50%)	12
Gait disturbance	2/10 (20%)	2	1/8 (12.5%)	2
Localized edema	1/10 (10%)	1	0/8 (0%)	0
Malaise	1/10 (10%)	1	0/8 (0%)	0
Pain	1/10 (10%)	3	1/8 (12.5%)	1
Immune system disorders
Allergic reaction	0/10 (0%)	0	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Bruising	1/10 (10%)	3	1/8 (12.5%)	1
Fall	1/10 (10%)	2	2/8 (25%)	2
Infusion related reaction	0/10 (0%)	0	1/8 (12.5%)	1
Investigations
Alanine aminotransferase increased	0/10 (0%)	0	1/8 (12.5%)	1
Aspartate aminotransferase increased	0/10 (0%)	0	1/8 (12.5%)	2
Creatinine increased	1/10 (10%)	1	1/8 (12.5%)	1
Lymphocyte count decreased	1/10 (10%)	1	0/8 (0%)	0
Platelet count decreased	1/10 (10%)	2	1/8 (12.5%)	8
Weight gain	0/10 (0%)	0	1/8 (12.5%)	1
Metabolism and nutrition disorders
Anorexia	1/10 (10%)	1	1/8 (12.5%)	1
Hyperglycemia	2/10 (20%)	3	1/8 (12.5%)	6
Hyperkalemia	0/10 (0%)	0	1/8 (12.5%)	2
Musculoskeletal and connective tissue disorders
Bone pain	1/10 (10%)	1	0/8 (0%)	0
Generalized muscle weakness	1/10 (10%)	1	0/8 (0%)	0
Muscle weakness lower limb	0/10 (0%)	0	1/8 (12.5%)	1
Musculoskeletal, conn tissue - Oth spec	0/10 (0%)	0	1/8 (12.5%)	1
Myalgia	0/10 (0%)	0	1/8 (12.5%)	4
Pain in extremity	1/10 (10%)	1	0/8 (0%)	0
Nervous system disorders
Dizziness	1/10 (10%)	2	1/8 (12.5%)	1
Dysarthria	1/10 (10%)	1	0/8 (0%)	0
Dysgeusia	0/10 (0%)	0	1/8 (12.5%)	2
Facial nerve disorder	1/10 (10%)	2	0/8 (0%)	0
Glossopharyngeal nerve disorder	1/10 (10%)	2	0/8 (0%)	0
Headache	1/10 (10%)	1	1/8 (12.5%)	1
Nervous system disorders - Oth spec	0/10 (0%)	0	1/8 (12.5%)	4
Seizure	1/10 (10%)	1	0/8 (0%)	0
Trigeminal nerve disorder	1/10 (10%)	1	0/8 (0%)	0
Psychiatric disorders
Depression	1/10 (10%)	1	0/8 (0%)	0
Renal and urinary disorders
Proteinuria	1/10 (10%)	1	2/8 (25%)	3
Urinary incontinence	0/10 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/10 (10%)	1	0/8 (0%)	0
Dyspnea	3/10 (30%)	6	0/8 (0%)	0
Hoarseness	1/10 (10%)	2	0/8 (0%)	0
Laryngeal inflammation	1/10 (10%)	1	0/8 (0%)	0
Nasal congestion	1/10 (10%)	1	1/8 (12.5%)	1
Vascular disorders
Hypertension	7/10 (70%)	43	7/8 (87.5%)	19
Hypotension	1/10 (10%)	2	2/8 (25%)	2
Thromboembolic event	1/10 (10%)	7	2/8 (25%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.