Trial Outcomes & Findings for The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors (NCT NCT01201850)

Results Overview

This pilot study was designed to evaluate the feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab. Patients enrolled on study were assessed for number of doses of bevacizumab that they received while on study. Participants who successfully received at least 5 of the 6 planned doses of bevacizumab (IV every 2 weeks) without significant events were determined to have met the outcome measure.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

7 participants

Primary outcome timeframe

13 weeks

Results posted on

2021-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab (Avastin®) Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Overall Study STARTED	7
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab (Avastin®) Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Overall Study Tumor progression	4

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab (Avastin®) n=7 Participants Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Age, Customized <10 yrs	3 participants n=7 Participants
Age, Customized >10 and <26 yrs	4 participants n=7 Participants
Sex: Female, Male Female	2 Participants n=7 Participants
Sex: Female, Male Male	5 Participants n=7 Participants

PRIMARY outcome

Timeframe: 13 weeks

Population: All patients who were enrolled/received a dose of bevacizumab were assessed.

This pilot study was designed to evaluate the feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab. Patients enrolled on study were assessed for number of doses of bevacizumab that they received while on study. Participants who successfully received at least 5 of the 6 planned doses of bevacizumab (IV every 2 weeks) without significant events were determined to have met the outcome measure.

Outcome measures

Outcome measures
Measure	Bevacizumab (Avastin®) n=7 Participants Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Number of Participants Who Received at Least 5 of the 6 Scheduled Doses of Bevacizumab	3 participants

SECONDARY outcome

Timeframe: 13 weeks

Population: Monitor overall neurologic status and symptoms before, during and 1 month following treatment with bevacizumab.

Outcome 1: Monitor overall neurologic status and symptoms before, during and 1 month following treatment with bevacizumab.

Outcome measures

Outcome measures
Measure	Bevacizumab (Avastin®) n=7 Participants Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Neurologic Status With Bevacizumab Treatment Neurologic improvement	4 participants
Neurologic Status With Bevacizumab Treatment No Neurologic improvement	3 participants

SECONDARY outcome

Timeframe: 13 weeks

Population: The dose and duration of corticosteroid use was collected and evaluated.

Outcome 2: Dose and duration of corticosteroid use prior to, during, and up to 1 month following bevacizumab treatment will also be collected and evaluated.

Outcome measures

Outcome measures
Measure	Bevacizumab (Avastin®) n=7 Participants Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Corticosteroid Usage With Bevacixumab Treatment Baseline Dexamethasone Dose (mg)	6.0 milligram Standard Deviation 4.0
Corticosteroid Usage With Bevacixumab Treatment End of therapy Dexamethasone dose (mg)	2.3 milligram Standard Deviation 5.2

SECONDARY outcome

Timeframe: 13 weeks

Population: The participant's quality of life as determined by the Modified McMaster Scale was evaluated at baseline, during and after treatment with bevacizumab

Outcome 3: To evaluate changes in quality of life before and after treatment with bevacizumab Modified McMasters Scale was used. Minimum score: 1 Maximum score 35. Higher score indicates worse quality of life.

Outcome measures

Outcome measures
Measure	Bevacizumab (Avastin®) n=7 Participants Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Changes in Quality of Life With Bevacizumab Treatment Baseline Modified McMasters Score	14.4 score on a scale Standard Deviation 3.6
Changes in Quality of Life With Bevacizumab Treatment End of therapy Modified McMasters Score	15.3 score on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: 13 weeks

Population: Descriptive report of radiographic changes with bevacizumab treatment

Outcome 4: To investigate the neuro-imaging changes in radiation necrosis associated edema, including Mass Resonance (MR) spectroscopy; MRIs (including FLAIR sequences and contrast enhanced images) were evaluated for changes in the radiation necrosis imaging characteristics by a pediatric radiologist. Decreases in gadolinium enhancement, FLAIR signal were considered changes consistent with decreased edema. Tumor size was also evaluated, with a decrease in tumor size indicating decreased edema/improved radiation necrosis

Outcome measures

Outcome measures
Measure	Bevacizumab (Avastin®) n=7 Participants Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Number of Patients With Changes in Neuro-Imaging With Bevacizumab Treatment Decreased gadolinium enhancement	7 Participants
Number of Patients With Changes in Neuro-Imaging With Bevacizumab Treatment Decreased FLAIR signal	5 Participants
Number of Patients With Changes in Neuro-Imaging With Bevacizumab Treatment Decreased tumor size	5 Participants

Adverse Events

Bevacizumab (Avastin®)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Bevacizumab (Avastin®) n=7 participants at risk Once enrolled, patients were treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Bevacizumab (Avastin®): bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses.
Investigations Aspartate aminotransferase increased	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Respiratory, thoracic and mediastinal disorders epistaxis	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Renal and urinary disorders proteinuria	28.6% 2/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Renal and urinary disorders renal and urinary disorders, other	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Musculoskeletal and connective tissue disorders back pain	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Gastrointestinal disorders mucositis	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Investigations lymphocyte count decreased	28.6% 2/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Investigations hypophosphatemia	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.
Investigations hypomagnesemia	14.3% 1/7 • 16 weeks (duration of trial and 30 days post last dose of bevacizumab) Adverse events that were possibly, probably or definitely related to study therapy were reported.

Additional Information

Margaret Macy, MD

Children's Hospital Colorado

Phone: 720-777-5877

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place