Trial Outcomes & Findings for Optune® Plus Bevacizumab in Bevacizumab-Refractory Recurrent Glioblastoma (NCT NCT02743078)

Last Updated: 2021-06-02

Results Overview

Number of participants alive at 6 months. Out of the planned 80 eligible patients, if 36 or more were alive at six months then the null hypothesis that the six-month survival rate is 35% or less would be rejected, concluding that the six-month survival is at least 35%. No testing was done due to the small number of participants resulting from early study closure.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

From registration to six months

Results posted on

2021-06-02

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab and TTFields Therapy Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Overall Study STARTED	3
Overall Study Eligible Populaton	3
Overall Study Eligible With Six-month Follow-up Data	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Optune® Plus Bevacizumab in Bevacizumab-Refractory Recurrent Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab and TTFields Therapy n=3 Participants Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Age, Continuous	55 years n=99 Participants
Sex: Female, Male Female	1 Participants n=99 Participants
Sex: Female, Male Male	2 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	2 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: From registration to six months

Population: Eligible with six-month follow-up data

Outcome measures

Outcome measures
Measure	Bevacizumab and TTFields Therapy n=3 Participants Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Overall Survival at 6 Months	1 Participants

SECONDARY outcome

Timeframe: From registration to study termination. Maximum follow-up was 21.8 months.

Survival time is defined as time from registration the to date of death from any cause or last known follow-up (censored) and was to be estimated by the Kaplan-Meier method. Given the small number of participants due to early study closure, only the number of patients last reported to be alive at time of study termination is reported.

Outcome measures

Outcome measures
Measure	Bevacizumab and TTFields Therapy n=3 Participants Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Overall Survival (OS)	1 Participants

SECONDARY outcome

Timeframe: From registration to study termination. Maximum follow-up was 21.8 months.

Progression is defined by the Modified Response Assessment in Neuro-Oncology (RANO) Response Criteria. (The precise definition is too long to be included here.) Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up. Progression-free survival rates were to be estimated using the Kaplan-Meier method. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without progression at time of study termination is reported.

Outcome measures

Outcome measures
Measure	Bevacizumab and TTFields Therapy n=3 Participants Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Progression-Free Survival	0 Participants

SECONDARY outcome

Timeframe: From registration to study termination. Maximum follow-up was 21.8 months.

Modified Response Assessment in Neuro-Oncology (RANO) Response Criteria was used to define response and progression. (The precise definitions are too long to be included here.) Objective response is defined as complete or partial response. The percentage of participants with objective response was to be estimated using the exact binomial method with accompanying 95% confidence intervals. Given the small number of participants due to early study closure, only the number of patients with objective response is reported.

Outcome measures

Outcome measures
Measure	Bevacizumab and TTFields Therapy n=3 Participants Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Number of Participants With Partial or Complete Response	0 Participants

SECONDARY outcome

Timeframe: From registration to study termination. Maximum follow-up was 21.8 months.

Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the adverse event (AE). The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. The percentage of participants with grade 3 or higher treatment-related adverse events was to be estimated using the exact binomial method with accompanying 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Bevacizumab and TTFields Therapy n=3 Participants Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Number of Participants With Grade 3+ Treatment-related Adverse Events	2 Participants

Adverse Events

Bevacizumab and TTFields Therapy

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab and TTFields Therapy n=3 participants at risk Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
Nervous system disorders Intracranial hemorrhage	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.

Other adverse events

Other adverse events
Measure	Bevacizumab and TTFields Therapy n=3 participants at risk Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation. Bevacizumab: 10 mg/kg every 2 weeks intravenously over 30 minutes. TTFields Therapy: Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.
General disorders Fatigue	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
General disorders Pain	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Infections and infestations Urinary tract infection	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Investigations Alanine aminotransferase increased	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Investigations Alkaline phosphatase increased	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Nervous system disorders Dysphasia	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Nervous system disorders Headache	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Psychiatric disorders Insomnia	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Renal and urinary disorders Proteinuria	33.3% 1/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	100.0% 3/3 • Every 28th day during treatment, at progression, then every 8 weeks for one year, then every 12 weeks for one year, then every 6 months. Maximum follow-up at time of study termination was 21.8 months.

Additional Information

Wendy Seiferheld

RTOG Foundation

Phone: 215-574-3208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER