Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM

Glioblastoma Multiforme Clinical Trial

— EF-32  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04471844
• Other study ID #: TRIDENT EF-32
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 8, 2020
• Est. completion date: August 2026

Study information

• Verified date: October 2023
• Source: NovoCure Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Optune® is a medical device that has been approved for the treatment of recurrent and newly diagnosed glioblastoma (GBM) by the Food and Drug Administration (FDA) in the United States. Optune® has obtained a CE mark in Europe for recurrent and newly diagnosed GBM. The current standard of care for GBM includes the addition of Optune® to maintenance temozolomide (TMZ), following the completion of radiation therapy (RT). The purpose of the current study is to test if the earlier introduction of Optune®, at the time of radiation therapy (which is given together with temozolomide), improves clinical outcomes compared to the standard of care. The study will randomize 950 subjects equally to one of two treatment arms: 1. Treatment arm I: Patients receive TTFields at 200 kHz to the brain using the Optune® System together with RT and TMZ, followed by maintenance TMZ concomitant with the Optune® treatment. 2. Treatment arm II: Patients receive RT and TMZ alone, followed by maintenance TMZ concomitant with TTFields at 200 kHz to the brain using the Optune®. All patients are to receive standard RT and TMZ treatment followed by maintenance TMZ chemotherapy and Optune® according to the current standard of care regimen. Optune® will continue until second disease progression per RANO Criteria or 24 months (the earlier of the two) unless any of the treatment discontinuation conditions described under criteria for patient withdrawal or termination are met. After surgery or biopsy, subjects that would like to participate will be required to submit samples of their tumor to a lab for testing. The results of this test will be used for randomization into the trial. If the subject is assigned to the treatment group that will start Optune® therapy during radiation therapy, Optune® therapy will begin within 7 days of enrolling in the study and no later than the first day of RT and TMZ treatment. After the initial visit, subjects will continue treatment at home, while pursuing normal daily routines. Subjects are required to use the device for at least 18 hours a day. Short breaks in treatment for personal hygiene and other personal needs is allowed. Total usage time will be recorded and provided to the sponsor. Subjects will be required to return to the clinic every 4 weeks until study participation ends. Once every 8 weeks until the tumor potentially returns twice, subjects will have a contrast MRI of the head and neurological exam performed for the first 6 months of the study and then at least every three months until a total time period of 24 months.Once every 12 weeks until second disease progression, subjects will also fill out a quality of life questionnaire. After the second time the tumor returns, subjects will return to the clinic for one final visit approximately 30 days after the last treatment with Optune®. After discontinuing Optune® subjects will be contacted once per month by telephone to answer basic questions about their health status.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 950
• Est. completion date: August 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Device:
• 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.

Locations

Country	Name	City	State
Austria	Innsbruck University Hospital	Innsbruck
Austria	Kepler University Hospital	Linz
Austria	University Hospital Salzburg	Salzburg
Belgium	Hospital Erasme	Brussels
Belgium	University Hospital Liege - Sart Tilman	Liège
Canada	CHUM Centre de Recherche	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Universite de Sherbrooke - Sherbrooke Centre Hospitalier Universita	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute - Odette Cancer Centre	Toronto	Ontario
Czechia	Masaryk Memorial Cancer Institute	Brno
Czechia	University Hospital Plzen	Pilsen
Czechia	Na Homolce Hospital	Prague
France	Institut de cancérologie de l'Ouest	Angers
France	Pierre Wertheimer Hospital	Bron
France	Hôpital la Timone	Marseille
France	University Hospital Nice	Nice
France	Pitié-Salpêtrière University Hospital	Paris
France	Institut de cancérologie de l'Ouest	Saint Herblain
France	University Institute Cancer Toulouse Oncopole	Toulouse
France	Gustave Roussy Institute	Villejuif
Germany	Charité Campus Virchow Clinic	Berlin
Germany	University Hospital Essen	Essen
Germany	University Medical Center Freiburg	Freiburg
Germany	University Hospital Leipzig	Leipzig
Germany	Rechts der Isar Hospital	Munich
Germany	University Hospital Tübingen	Tübingen
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center - Ein Kerem	Jerusalem
Israel	Rabin Medical Center	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Japan	Saitama Medical University International Medical Center	Hidaka-shi	Saitama-Ken
Japan	Kanazawa University Hospital	Kanazawa-shi	Ishikawa-Ken
Japan	Kyorin University Hospital	Mitaka-shi	Tokyo-To
Japan	Hokkaido University Hospital	Sapporo-shi	Hokkaido
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo-To
Switzerland	Lausanne University Hospital	Lausanne
Switzerland	University Hospital Zurich	Zürich
United Kingdom	Clatterbridge Cancer Centre	Liverpool
United Kingdom	Charing Cross Hospital	London
United Kingdom	Guy's Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Royal Preston Hospital	Preston
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northside Hospital, Inc.	Atlanta	Georgia
United States	Piedmont Healthcare Brain Tumor Center	Atlanta	Georgia
United States	The Emory Clinic - Emory Healthcare - Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Cancer Center Anschutz	Aurora	Colorado
United States	Texas Oncology Midtown - Austin Brain Tumor Center	Austin	Texas
United States	John Hopkins School of Medicine	Baltimore	Maryland
United States	Grandview Cancer Center	Birmingham	Alabama
United States	Lynn Cancer Institute, Marcus Neuroscience Institute	Boca Raton	Florida
United States	Tufts Medical Center	Boston	Massachusetts
United States	The University of Vermont Medical Center - University of Vermont Cancer Center	Burlington	Vermont
United States	University of North Carolina Brain Tumor Program - UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	MUSC Radiation Oncology Brain & Spine Tumor Program	Charleston	South Carolina
United States	Novant Health Cancer Institute Radiation Oncology	Charlotte	North Carolina
United States	SCRI - Tennessee Oncology	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	University of Missouri - Ellis Fischel Cancer Center	Columbia	Missouri
United States	The James Cancer Hospital and Solove Research Institute - Arthur G James Cancer Hospital	Columbus	Ohio
United States	Baylor Charles A. Sammons Cancer Center - Baylor University Medical Center	Dallas	Texas
United States	Geisinger Health System	Danville	Pennsylvania
United States	City of Hope National Medical Center	Duarte	California
United States	JFK Neuroscience Institute, HMH JFK University Medical Center	Edison	New Jersey
United States	HCA Research Institute - Blue Sky Neurology - Denver	Englewood	Colorado
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Parkview Cancer Institute - Fort Wayne Radiation Oncology Associates	Fort Wayne	Indiana
United States	John Peter Smith Health Network - JPS Cancer Center	Fort Worth	Texas
United States	TRIO - St. Jude Heritage Healthcare/St. Jude Medical Center	Fullerton	California
United States	West Cancer Center - Germantown	Germantown	Tennessee
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Vidant Medical Center	Greenville	North Carolina
United States	Hackensack University Medical Center - John Theurer Cancer Center	Hackensack	New Jersey
United States	Houston Methodist Hospital	Houston	Texas
United States	UT Health Mischer Neuroscience - Memorial Herman - UT Neurosciences	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist Health - Jacksonville	Jacksonville	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	Health Midwest Ventures Group, Inc - Sarah Cannon HCA Midwest Brain and Spine	Kansas City	Missouri
United States	University of California at San Diego - Moores Cancer Center	La Jolla	California
United States	Northwell Health System Brain Tumor Center	Lake Success	New York
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cedars - Sinai Medical Center	Los Angeles	California
United States	Norris Comprehensive Cancer Center at USC	Los Angeles	California
United States	Providence St. Joseph Medical Center and The Roy and Patricia Disney Family Cancer Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky
United States	Abbott Northwestern Hospital - Givens Brain Tumor Center	Minneapolis	Minnesota
United States	University of Minnesota Health Clinics and Surgery Center	Minneapolis	Minnesota
United States	West Virginia University Cancer Institute	Morgantown	West Virginia
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Hartford Healthcare Medical Group - Hartford Hospital The Gray Cancer Center	New London	Connecticut
United States	LSU Health Sciences Center, New Orleans	New Orleans	Louisiana
United States	Ochsner Health System	New Orleans	Louisiana
United States	Mount Sinai - Icahn School of Medicine	New York	New York
United States	New York Presbyterian - Columbia University	New York	New York
United States	NYU Langone - Laura & Issac Perimutter Cancer Center	New York	New York
United States	Hoag Memorial Hospital - Hoag Cancer Center	Newport Beach	California
United States	St. Joseph Hospital of Orange	Orange	California
United States	University of California - Irvine/UCI Medical Center	Orange	California
United States	AdventHealth	Orlando	Florida
United States	Orlando Health UF Health Cancer Center	Orlando	Florida
United States	The University of Kansas Cancer Center	Overland Park	Kansas
United States	Stanford University Cancer Institute	Palo Alto	California
United States	Neuroscience Center, Philadelphia University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic- Arizona	Phoenix	Arizona
United States	Allegheny Health Network Cancer Institute	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Massey Cancer Center - VCU Medical Center	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	San Antonio Cancer Institute	San Antonio	Texas
United States	Sharp Memorial Hospital - X-Ray Medical Group Radiation Oncology	San Diego	California
United States	University of California San Francisco Medical Center	San Francisco	California
United States	John Wayne Cancer Institute at St. John's Health Center	Santa Monica	California
United States	Swedish Health Services	Seattle	Washington
United States	UW Medical Center - Alvord Brain Tumor Center	Seattle	Washington
United States	Maine Medical Partners Neurology - Neurosurgery & Spine Associates	South Portland	Maine
United States	SUNY Upstate Medical University	Syracuse	New York
United States	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida
United States	Baylor Scott & White Medical Center	Temple	Texas
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Forsyth Medical Center-Novant Health	Winston-Salem	North Carolina
United States	Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
NovoCure GmbH

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Israel,  Japan,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Survival will be measured from the time of randomization until date patient is alive.	5 years
Secondary	Progression Free Survival (PFS)	PFS will be measured from the date of randomization to the date of progression.	5 years
Secondary	1- and 2-year survival rates	The analyses will be performed based on estimated proportions of patients who are on study at 12 and 24 months in both arms of the study.	5 years
Secondary	Overall Radiological response (ORR)	The analyses will be performed based on the RANO criteria, and comparison between the rates of response.	5 years
Secondary	Next progression-free survival (PFS2)	PFS2 will be measured from the time of randomization to second tumor progression.	5 years
Secondary	Progression-free survival at 6 (PFS6) and 12 months (PFS12)	The analyses will be estimated proportions of patients who are progression-free at 6 and 12 months in both arms of the study.	5 years
Secondary	Severity and frequency of adverse events	The analyses will be performed based on the incidence, severity, frequency of adverse events, and their association with study treatments.	5 years
Secondary	Pathological changes in resected GBM tumors following study treatments	Pathological changes in the tumors and also underwent another surgical resection while on the study.	5 years
Secondary	Quality of Life EORTC Questionnaire	The analyses will be assessed using the EORTC QLQ C-30 questionnaire with BN-20 (brain symptom) supplement.	5 years
Secondary	Dependence of overall survival on TTFields dose at the tumor	Examining the dependence of overall survival on TTFields dose delivered to the tumor bed will be performed in both the treatment and control arms.	5 years
Secondary	The NANO scale	The Neurological assessment in Neuro-Oncology will be assessed using the NANO scale questionnaire and per RANO criteria.	5 years