Trial Outcomes & Findings for Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases (NCT NCT02490878)

Last Updated: 2023-03-23

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Baseline, 2, 4, 6 and 8 weeks

Results posted on

2023-03-23

Participant Flow

40 patients underwent pre-screening. Only 19 underwent randomization.

Participant milestones

Participant milestones
Measure	Arm A: Bevacizumab 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.	Arm B: Placebo 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.
Overall Study STARTED	10	9
Overall Study Eligible Participants	10	8
Overall Study COMPLETED	10	6
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Bevacizumab 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.	Arm B: Placebo 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.
Overall Study deemed ineligible	0	1
Overall Study progression prior to treatment	0	1
Overall Study only submitted baseline QOL	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=6 Participants 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 n=16 Participants Total of all reporting groups
Age, Customized Age group · <= 65 years	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Age, Customized Age group · > 65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Prior whole brain radiotherapy Yes	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Prior whole brain radiotherapy No	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

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

Population: 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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=6 Participants 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.
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score 2 weeks	-0.8 score on a scale Standard Deviation 1.93	0.1 score on a scale Standard Deviation 1.24
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score 4 weeks	-0.5 score on a scale Standard Deviation 2.17	-2.0 score on a scale Standard Deviation 2.53
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score 6 weeks	-0.5 score on a scale Standard Deviation 2.33	-2.3 score on a scale Standard Deviation 2.86
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score 8 weeks	-0.6 score on a scale Standard Deviation 2.13	-3.9 score on a scale Standard Deviation 2.83

SECONDARY outcome

Timeframe: Up to 1.5 years post-treatment

Population: All patients that began treatment are included in this endpoint

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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=8 Participants 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.
Toxicity (CTCAE Version 4.0) Grade 3 or higher	2 Participants	5 Participants
Toxicity (CTCAE Version 4.0) Grade 4 or higher	0 Participants	0 Participants
Toxicity (CTCAE Version 4.0) Grade 5	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 1.5 years post-treatment

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

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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=8 Participants 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.	Arm B: Placebo n=5 Participants 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.
Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) LASA Overall Quality of Life	-1.0 score on a scale Standard Deviation 3.07	0.0 score on a scale Standard Deviation 2.55
Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) LASA Mental well being	-1.5 score on a scale Standard Deviation 3.12	0.0 score on a scale Standard Deviation 1.73
Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) LASA Physical well being	-1.1 score on a scale Standard Deviation 3.4	0.4 score on a scale Standard Deviation 1.14
Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) LASA Emotional well being	-1.0 score on a scale Standard Deviation 2.45	1.8 score on a scale Standard Deviation 3.03
Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) LASA Spiritual well being	-1.1 score on a scale Standard Deviation 2.42	0.8 score on a scale Standard Deviation 2.17

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=7 Participants 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.
Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) Baseline	1.0 score on a scale Standard Deviation 0.15	1.2 score on a scale Standard Deviation 0.33
Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) Week 2	1.0 score on a scale Standard Deviation 0.14	1.2 score on a scale Standard Deviation 0.23
Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) Week 4	1.0 score on a scale Standard Deviation 0.14	1.0 score on a scale Standard Deviation 0.14
Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) Week 6	1.0 score on a scale Standard Deviation 0.07	1.0 score on a scale Standard Deviation 0.07
Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) Week 8	1.0 score on a scale Standard Deviation 0.15	1.0 score on a scale Standard Deviation 0.16

SECONDARY outcome

Timeframe: Up to 1.5 years post-treatment

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

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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=6 Participants 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.
Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. Baseline	4.0 score on a scale Standard Deviation 1.51	5.3 score on a scale Standard Deviation 2.27
Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. Week 2	2.9 score on a scale Standard Deviation 2.39	6.1 score on a scale Standard Deviation 0.88
Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. Week 4	3.9 score on a scale Standard Deviation 2.75	4.8 score on a scale Standard Deviation 1.73
Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. Week 6	3.9 score on a scale Standard Deviation 2.21	4.9 score on a scale Standard Deviation 3.29
Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. Week 8	4.0 score on a scale Standard Deviation 2.44	4.3 score on a scale Standard Deviation 3.06

SECONDARY outcome

Timeframe: Up to 16 weeks

Population: All patients that registered were included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=9 Participants 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.
Progression Free Survival	NA days Too few events have been reported to obtain a median or estimate a 95% Confidence Interval	NA days Interval 103.0 to Too few events have been reported to obtain a median or estimate an upper level 95% Confidence Interval

SECONDARY outcome

Timeframe: Up to 16 weeks

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

Time from start of treatment to maximum radiographic response

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 16 weeks

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

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.

Outcome measures

Outcome measures
Measure	Arm A: Bevacizumab n=10 Participants 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.	Arm B: Placebo n=9 Participants 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.
Time to Stopping Corticosteroids	113 days Interval 50.0 to 141.0	102 days Interval 29.0 to 252.0

Adverse Events

Arm A: Bevacizumab

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Arm B: Placebo

Serious events: 6 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Caroline Chung, MD

MD Anderson Cancer Center

Phone: (713) 745-5422

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A: Bevacizumab n=10 participants at risk 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.	Arm B: Placebo n=8 participants at risk 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.
General disorders Fever	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Infections and infestations Infections and infestations - Oth spec	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Infections and infestations Lung infection	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Infections and infestations Sepsis	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Alanine aminotransferase increased	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations CPK increased	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Metabolism and nutrition disorders Hyperglycemia	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	25.0% 2/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Depressed level of consciousness	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Dysgeusia	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Dysphasia	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Headache	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Seizure	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	25.0% 2/8 • Number of events 3 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Psychiatric disorders Confusion	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Vascular disorders Thromboembolic event	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.

Measure	Arm A: Bevacizumab n=10 participants at risk 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.	Arm B: Placebo n=8 participants at risk 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.
Blood and lymphatic system disorders Anemia	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 6 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Endocrine disorders Cushingoid	10.0% 1/10 • Number of events 3 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Eye disorders Blurred vision	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Gastrointestinal disorders Dry mouth	10.0% 1/10 • Number of events 4 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Gastrointestinal disorders Dysphagia	20.0% 2/10 • Number of events 4 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Gastrointestinal disorders Gastrointestinal disorders - Oth spec	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Gastrointestinal disorders Nausea	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Gastrointestinal disorders Stomach pain	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
General disorders Chills	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
General disorders Fatigue	40.0% 4/10 • Number of events 12 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	50.0% 4/8 • Number of events 12 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
General disorders Gait disturbance	20.0% 2/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
General disorders Localized edema	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
General disorders Malaise	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
General disorders Pain	10.0% 1/10 • Number of events 3 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Immune system disorders Allergic reaction	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Injury, poisoning and procedural complications Bruising	10.0% 1/10 • Number of events 3 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Injury, poisoning and procedural complications Fall	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	25.0% 2/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Alanine aminotransferase increased	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Aspartate aminotransferase increased	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Creatinine increased	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Lymphocyte count decreased	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Platelet count decreased	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Investigations Weight gain	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Metabolism and nutrition disorders Anorexia	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Metabolism and nutrition disorders Hyperglycemia	20.0% 2/10 • Number of events 3 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 6 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Musculoskeletal, conn tissue - Oth spec	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 4 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Dizziness	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Dysarthria	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Dysgeusia	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Facial nerve disorder	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Glossopharyngeal nerve disorder	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Headache	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Nervous system disorders - Oth spec	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 4 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Seizure	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Nervous system disorders Trigeminal nerve disorder	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Psychiatric disorders Depression	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Renal and urinary disorders Proteinuria	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	25.0% 2/8 • Number of events 3 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Renal and urinary disorders Urinary incontinence	0.00% 0/10 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	30.0% 3/10 • Number of events 6 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Respiratory, thoracic and mediastinal disorders Hoarseness	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	0.00% 0/8 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 1/10 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	12.5% 1/8 • Number of events 1 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Vascular disorders Hypertension	70.0% 7/10 • Number of events 43 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	87.5% 7/8 • Number of events 19 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Vascular disorders Hypotension	10.0% 1/10 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	25.0% 2/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.
Vascular disorders Thromboembolic event	10.0% 1/10 • Number of events 7 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.	25.0% 2/8 • Number of events 2 • Adverse events were collected on days 1 and 15 during 4 cycles of treatment. Each cycle was 28 days.