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

NCT ID: NCT04471844

Last Updated: 2025-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

981 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-08

Study Completion Date

2026-01-30

Brief Summary

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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.

Detailed Description

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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 2010 RANO Criteria 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 10 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 site and sponsor.

Subjects will be required to return to the clinic per the study protocol.

After the second disease progression, subjects will return to the clinic for one final visit approximately 30 days after the last treatment with Optune® or after second disease progression, the latter of the two per protocol.

After completing active participation in the study, subjects will be contacted once per month to answer basic questions about their health status.

Conditions

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Glioblastoma Multiforme

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomly assigned equally to one of two groups:

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®.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Optune®

Intervention Type DEVICE

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.

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.

Group Type ACTIVE_COMPARATOR

Optune®

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed diagnosis of GBM according to WHO 2016 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 β-HCG pregnancy test documented within 14 days prior to randomization
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. Additional malignancies that are progressing or required active treatment in the last two years.
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 put the participant at risk according to the investigator.

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NovoCure Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Grandview Cancer Center

Birmingham, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Mayo Clinic- Arizona

Phoenix, Arizona, United States

Site Status

University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Providence St. Joseph Medical Center and The Roy and Patricia Disney Family Cancer Center

Burbank, California, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

TRIO - St. Jude Heritage Healthcare/St. Jude Medical Center

Fullerton, California, United States

Site Status

University of California at San Diego - Moores Cancer Center

La Jolla, California, United States

Site Status

Norris Comprehensive Cancer Center at USC

Los Angeles, California, United States

Site Status

Cedars - Sinai Medical Center

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital - Hoag Cancer Center

Newport Beach, California, United States

Site Status

St. Joseph Hospital of Orange

Orange, California, United States

Site Status

University of California - Irvine/UCI Medical Center

Orange, California, United States

Site Status

Stanford University Cancer Institute

Palo Alto, California, United States

Site Status

Sharp Memorial Hospital - X-Ray Medical Group Radiation Oncology

San Diego, California, United States

Site Status

University of California San Francisco Medical Center

San Francisco, California, United States

Site Status

John Wayne Cancer Institute at St. John's Health Center

Santa Monica, California, United States

Site Status

University of Colorado Cancer Center Anschutz

Aurora, Colorado, United States

Site Status

HCA Research Institute - Blue Sky Neurology - Denver

Englewood, Colorado, United States

Site Status

Hartford Healthcare Medical Group - Hartford Hospital The Gray Cancer Center

Hartford, Connecticut, United States

Site Status

Lynn Cancer Institute, Marcus Neuroscience Institute

Boca Raton, Florida, United States

Site Status

Baptist Health - Jacksonville

Jacksonville, Florida, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

AdventHealth

Orlando, Florida, United States

Site Status

Orlando Health UF Health Cancer Center

Orlando, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

Site Status

Piedmont Healthcare Brain Tumor Center

Atlanta, Georgia, United States

Site Status

The Emory Clinic - Emory Healthcare - Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Northside Hospital, Inc.

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Parkview Cancer Institute - Fort Wayne Radiation Oncology Associates

Fort Wayne, Indiana, United States

Site Status

The University of Kansas Cancer Center

Topeka, Kansas, United States

Site Status

University of Louisville - James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Mary Bird Cancer Center Neuromedical Center

Baton Rouge, Louisiana, United States

Site Status

LSU Health Sciences Center, New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Health System

New Orleans, Louisiana, United States

Site Status

Maine Medical Partners Neurology - Neurosurgery & Spine Associates

South Portland, Maine, United States

Site Status

John Hopkins School of Medicine

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

University of Massachusetts Chan Medical School

Worcester, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Abbott Northwestern Hospital - Givens Brain Tumor Center

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Missouri - Ellis Fischel Cancer Center

Columbia, Missouri, United States

Site Status

Health Midwest Ventures Group, Inc - Sarah Cannon HCA Midwest Brain and Spine

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

JFK Neuroscience Institute, HMH JFK University Medical Center

Edison, New Jersey, United States

Site Status

Hackensack University Medical Center - John Theurer Cancer Center

Hackensack, New Jersey, United States

Site Status

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status

Northwell Health System Brain Tumor Center

Lake Success, New York, United States

Site Status

NYU Langone - Laura & Issac Perimutter Cancer Center

New York, New York, United States

Site Status

Mount Sinai - Icahn School of Medicine

New York, New York, United States

Site Status

New York Presbyterian - Columbia University

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

University of North Carolina Brain Tumor Program - UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Novant Health Cancer Institute Radiation Oncology

Charlotte, North Carolina, United States

Site Status

Vidant Medical Center

Greenville, North Carolina, United States

Site Status

Forsyth Medical Center-Novant Health

Winston-Salem, North Carolina, United States

Site Status

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Site Status

The James Cancer Hospital and Solove Research Institute - Arthur G James Cancer Hospital

Columbus, Ohio, United States

Site Status

Oregon Health & Science University (OHSU)

Portland, Oregon, United States

Site Status

Neuroscience Center, Philadelphia - University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Allegheny Health Network Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

MUSC Radiation Oncology Brain & Spine Tumor Program

Charleston, South Carolina, United States

Site Status

SCRI - Tennessee Oncology

Chattanooga, Tennessee, United States

Site Status

West Cancer Center - Germantown

Germantown, Tennessee, United States

Site Status

SCRI - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Texas Oncology Midtown - Austin Brain Tumor Center

Austin, Texas, United States

Site Status

Baylor Charles A. Sammons Cancer Center - Baylor University Medical Center

Dallas, Texas, United States

Site Status

John Peter Smith Health Network - JPS Cancer Center

Fort Worth, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

UT Health Mischer Neuroscience - Memorial Herman - UT Neurosciences

Houston, Texas, United States

Site Status

Baylor Scott & White Medical Center

Temple, Texas, United States

Site Status

The University of Vermont Medical Center - University of Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Massey Cancer Center - VCU Medical Center

Richmond, Virginia, United States

Site Status

UW Medical Center - Alvord Brain Tumor Center

Seattle, Washington, United States

Site Status

Swedish Health Services

Seattle, Washington, United States

Site Status

West Virginia University Cancer Institute

Morgantown, West Virginia, United States

Site Status

Innsbruck University Hospital

Innsbruck, , Austria

Site Status

Kepler University Hospital

Linz, , Austria

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University Hospital Salzburg

Salzburg, , Austria

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Hospital Erasme

Brussels, , Belgium

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University Hospital Liege - Sart Tilman

Liège, , Belgium

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BC Cancer - Vancouver

Vancouver, British Columbia, Canada

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Nova Scotia Health Authority

Sydney, Nova Scotia, Canada

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The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

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Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Sunnybrook Research Institute - Odette Cancer Centre

Toronto, Ontario, Canada

Site Status

CHUM Centre de Recherche

Montreal, Quebec, Canada

Site Status

Universite de Sherbrooke - Sherbrooke Centre Hospitalier Universita

Sherbrooke, Quebec, Canada

Site Status

Masaryk Memorial Cancer Institute

Brno, , Czechia

Site Status

University Hospital Plzeň

Pilsen, , Czechia

Site Status

Na Homolce Hospital

Prague, , Czechia

Site Status

Institut de cancérologie de l'Ouest

Angers, , France

Site Status

Pierre Wertheimer Hospital

Bron, , France

Site Status

Hôpital la Timone

Marseille, , France

Site Status

University Hospital Nice

Nice, , France

Site Status

Pitié-Salpêtrière University Hospital

Paris, , France

Site Status

Institut de cancérologie de l'Ouest

Saint-Herblain, , France

Site Status

University Institute Cancer Toulouse Oncopole

Toulouse, , France

Site Status

Gustave Roussy Institute

Villejuif, , France

Site Status

Charité Campus Virchow Clinic

Berlin, , Germany

Site Status

University Hospital Essen

Essen, , Germany

Site Status

University Medical Center Freiburg

Freiburg im Breisgau, , Germany

Site Status

University Hospital Leipzig

Leipzig, , Germany

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Rechts der Isar Hospital

Munich, , Germany

Site Status

University Hospital Tübingen

Tübingen, , Germany

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Hadassah Medical Center - Ein Kerem

Jerusalem, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Site Status

Saitama Medical University International Medical Center

Hidaka-shi, Saitama, Japan

Site Status

Kyorin University Hospital

Mitaka-shi, Tokyo-To, Japan

Site Status

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo-To, Japan

Site Status

Lausanne University Hospital

Lausanne, , Switzerland

Site Status

University Hospital Zurich

Zurich, , Switzerland

Site Status

Clatterbridge Cancer Centre

Liverpool, , United Kingdom

Site Status

Guy's Hospital

London, , United Kingdom

Site Status

Charing Cross Hospital

London, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Royal Preston Hospital

Preston, , United Kingdom

Site Status

Countries

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

References

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Miller R, Niazi M, Russial O, Poiset S, Shi W. Tumor treating fields with radiation for glioblastoma: a narrative review. Chin Clin Oncol. 2022 Oct;11(5):40. doi: 10.21037/cco-22-90.

Reference Type DERIVED
PMID: 36336899 (View on PubMed)

Miller R, Song A, Ali A, Niazi M, Bar-Ad V, Martinez N, Glass J, Alnahhas I, Andrews D, Judy K, Evans J, Farrell C, Werner-Wasik M, Chervoneva I, Ly M, Palmer J, Liu H, Shi W. Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma. Front Oncol. 2022 Apr 29;12:896246. doi: 10.3389/fonc.2022.896246. eCollection 2022.

Reference Type DERIVED
PMID: 35574391 (View on PubMed)

Other Identifiers

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TRIDENT EF-32

Identifier Type: -

Identifier Source: org_study_id

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