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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04471844




Registration number
NCT04471844
Ethics application status
Date submitted
9/07/2020
Date registered
15/07/2020
Date last updated
26/02/2024

Titles & IDs
Public title
Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM
Scientific title
EF-32: Pivotal, Randomized, Open-Label Study of Optune® (Tumor Treating Fields, 200kHz) Concomitant With Radiation Therapy and Temozolomide for the Treatment of Newly Diagnosed Glioblastoma
Secondary ID [1] 0 0
TRIDENT EF-32
Universal Trial Number (UTN)
Trial acronym
EF-32
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma Multiforme 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BI 754091
Treatment: Devices - Optune®

Experimental: Optune® + RT + TMZ for 6 weeks - Optune® + RT + TMZ for 6 weeks, followed by Optune® + TMZ until the tumor progresses. Optune treatment is maintained until second disease progression or 24 months.

Active comparator: RT +TMZ for 6 weeks - RT +TMZ for 6 weeks followed by Optune® + TMZ until the tumor progresses. Optune treatment is maintained until second disease progression or 24 months.


Treatment: Drugs: BI 754091
BI 754091

Treatment: Devices: Optune®
Optune® is a commercial, portable, battery-operated device intended for continuous home use, which delivers TTFields at a frequency of 200kHz to the brain by means of insulated transducer arrays. The Optune® device produces electric forces intended to disrupt cancer cell division.

In treatment arm I, the patient starts Optune® concurrently with RT/TMZ for 6 weeks, followed by Optune® + TMZ until second disease progression.

In treatment arm II, the patient starts RT/TMZ for 6 weeks, followed by Optune® + TMZ until second disease progression.

The study treatment plan will continue for 24 months, if no tumor progression.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
1- and 2-year survival rates
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Overall Radiological response (ORR)
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Next progression-free survival (PFS2)
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Progression-free survival at 6 (PFS6) and 12 months (PFS12)
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Severity and frequency of adverse events
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Pathological changes in resected GBM tumors following study treatments
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
Quality of Life EORTC Questionnaire
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Dependence of overall survival on TTFields dose at the tumor
Timepoint [9] 0 0
5 years
Secondary outcome [10] 0 0
The NANO scale
Timepoint [10] 0 0
5 years

Eligibility
Key inclusion criteria
1. Histologically confirmed diagnosis of GBM according to WHO classification criteria.
2. Age = 22 years in US and Age = 18 years in Ex-US
3. Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
4. Planned treatment with RT/TMZ followed by TTFields and maintenance TMZ (150-200 mg/m2 daily x 5 d, q28 days)
5. Karnofsky performance status = 70
6. Life expectancy = least 3 months
7. Participants of childbearing age must use highly effective contraception. An effective method of birth control is defined as one that results in a failure rate of less than 1% per year when used consistently and correctly. The Investigator must approve the selected method, and may consult with a gynecologist as needed.
8. All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
9. Stable or decreasing dose of corticosteroids for the last 7 days prior to randomization, if applicable.
10. Concomitant RT with TMZ treatment planned to start no later than 8 weeks from surgery
11. Women of childbearing potential must have a negative ß-HCG pregnancy test documented within 14 days prior to registration
12. Is able to have MRI with contrast of the brain
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Progressive disease (per investigator's assessment)
2. Infratentorial or leptomeningeal disease
3. Participation in another clinical treatment study during the pre-treatment and/or the treatment phase of the study
4. Pregnancy or breast-feeding.
5. Significant co-morbidities at baseline which would preclude maintenance RT or TMZ treatment, as determined by the investigator:

1. Thrombocytopenia (platelet count < 100 x 103/µL)
2. Neutropenia (absolute neutrophil count < 1.5 x 103/µL)
3. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
4. Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
5. Total bilirubin > 1.5 x upper limit of normal
6. Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l)
7. History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
6. Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
7. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
8. History of hypersensitivity reaction to TMZ or a history of hypersensitivity to DTIC.
9. Any other cytotoxic or biologic anti-tumor therapy received prior to enrollment will be considered exclusion.
10. Admitted to an institution by administrative or court order.
11. Known allergies to medical adhesives or hydrogel
12. A skull defect (such as, missing bone with no replacement)
13. Prior radiation treatment to the brain for the treatment of GBM
14. Any serious surgical/post-operative condition that may risk the patient according to the investigator
15. Standard TTFields exclusion criteria include

1. Active implanted medical devices
2. Bullet fragments
3. Skull defects

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
950
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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Arkansas
Country [4] 0 0
United States of America
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California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
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Connecticut
Country [7] 0 0
United States of America
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Florida
Country [8] 0 0
United States of America
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Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
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State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
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United States of America
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Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maine
Country [15] 0 0
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State/province [15] 0 0
Maryland
Country [16] 0 0
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Massachusetts
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Michigan
Country [18] 0 0
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Minnesota
Country [19] 0 0
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Mississippi
Country [20] 0 0
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Missouri
Country [21] 0 0
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New Hampshire
Country [22] 0 0
United States of America
State/province [22] 0 0
New Jersey
Country [23] 0 0
United States of America
State/province [23] 0 0
New York
Country [24] 0 0
United States of America
State/province [24] 0 0
North Carolina

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
NovoCure GmbH
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To test the effectiveness and safety of Optune® given concomitantly with radiation therapy (RT) and temozolomide (TMZ) in newly diagnosed GBM patients, compared to radiation therapy and temozolomide alone. In both arms, Optune® and maintenance temozolomide are continued following radiation therapy.
Trial website
https://clinicaltrials.gov/study/NCT04471844
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Doron Manzur, MD
Address 0 0
Country 0 0
Phone 0 0
+1 603 206 2337
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04471844