Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant with RT & TMZ for the Treatment of Newly Diagnosed GBM
- Conditions
- Glioblastoma Multiforme
- Interventions
- Device: Optune®
- Registration Number
- NCT04471844
- Lead Sponsor
- NovoCure Ltd.
- 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.
- Detailed 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 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 by telephone to answer basic questions about their health status.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 982
- Histologically confirmed diagnosis of GBM according to WHO classification criteria.
- Age ≥ 22 years in US and Age ≥ 18 years in Ex-US
- Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
- Planned treatment with RT/TMZ followed by TTFields and maintenance TMZ (150-200 mg/m2 daily x 5 d, q28 days)
- Karnofsky performance status ≥ 70
- Life expectancy ≥ least 3 months
- 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.
- All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
- Stable or decreasing dose of corticosteroids for the last 7 days prior to randomization, if applicable.
- Concomitant RT with TMZ treatment planned to start no later than 8 weeks from surgery
- Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days prior to randomization
- Is able to have MRI with contrast of the brain
-
Progressive disease (per investigator's assessment)
-
Infratentorial or leptomeningeal disease
-
Participation in another clinical treatment study during the pre-treatment and/or the treatment phase of the study
-
Pregnancy or breast-feeding.
-
Significant co-morbidities at baseline which would preclude maintenance RT or TMZ treatment, as determined by the investigator:
- Thrombocytopenia (platelet count < 100 x 103/μL)
- Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
- CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
- Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
- Total bilirubin > 1.5 x upper limit of normal
- Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l)
- 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
-
Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
-
Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
-
History of hypersensitivity reaction to TMZ or a history of hypersensitivity to DTIC.
-
Additional malignancies that are progressing or required active treatment in the last two years.
-
Admitted to an institution by administrative or court order.
-
Known allergies to medical adhesives or hydrogel
-
A skull defect (such as, missing bone with no replacement)
-
Prior radiation treatment to the brain for the treatment of GBM
-
Any serious surgical/post-operative condition that may put the participant at risk according to the investigator.
-
Standard TTFields exclusion criteria include
- Active implanted medical devices
- Bullet fragments
- Skull defects
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Optune® + RT + TMZ for 6 weeks Optune® 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. 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 5 years Survival will be measured from the time of randomization until date patient is alive.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 5 years PFS will be measured from the date of randomization to the date of progression.
1- and 2-year survival rates 5 years 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.
Next progression-free survival (PFS2) 5 years PFS2 will be measured from the time of randomization to second tumor progression.
Overall Radiological response (ORR) 5 years The analyses will be performed based on the RANO criteria, and comparison between the rates of response.
Progression-free survival at 6 (PFS6) and 12 months (PFS12) 5 years The analyses will be estimated proportions of patients who are progression-free at 6 and 12 months in both arms of the study.
Quality of Life EORTC Questionnaire 5 years The analyses will be assessed using the EORTC QLQ C-30 questionnaire with BN-20 (brain symptom) supplement.
Severity and frequency of adverse events 5 years The analyses will be performed based on the incidence, severity, frequency of adverse events, and their association with study treatments.
Pathological changes in resected GBM tumors following study treatments 5 years Pathological changes in the tumors and also underwent another surgical resection while on the study.
Dependence of overall survival on TTFields dose at the tumor 5 years Examining the dependence of overall survival on TTFields dose delivered to the tumor bed will be performed in both the treatment and control arms.
The NANO scale 5 years The Neurological assessment in Neuro-Oncology will be assessed using the NANO scale questionnaire and per RANO criteria.
Trial Locations
- Locations (131)
Mary Bird Cancer Center Neuromedical Center
🇺🇸Baton Rouge, Louisiana, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
Neuroscience Center, Philadelphia - University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
BC Cancer - Vancouver
🇨🇦Vancouver, British Columbia, Canada
Nova Scotia Health Authority
🇨🇦Sydney, Nova Scotia, Canada
Grandview Cancer Center
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic- Arizona
🇺🇸Phoenix, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Providence St. Joseph Medical Center and The Roy and Patricia Disney Family Cancer Center
🇺🇸Burbank, California, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
TRIO - St. Jude Heritage Healthcare/St. Jude Medical Center
🇺🇸Fullerton, California, United States
University of California at San Diego - Moores Cancer Center
🇺🇸La Jolla, California, United States
Norris Comprehensive Cancer Center at USC
🇺🇸Los Angeles, California, United States
Cedars - Sinai Medical Center
🇺🇸Los Angeles, California, 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
Stanford University Cancer Institute
🇺🇸Palo Alto, California, 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
University of Colorado Cancer Center Anschutz
🇺🇸Aurora, Colorado, United States
HCA Research Institute - Blue Sky Neurology - Denver
🇺🇸Englewood, Colorado, United States
Hartford Healthcare Medical Group - Hartford Hospital The Gray Cancer Center
🇺🇸Hartford, Connecticut, United States
Lynn Cancer Institute, Marcus Neuroscience Institute
🇺🇸Boca Raton, Florida, United States
Baptist Health - Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
AdventHealth
🇺🇸Orlando, Florida, United States
Orlando Health UF Health Cancer Center
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
🇺🇸Tampa, Florida, United States
Piedmont Healthcare Brain Tumor Center
🇺🇸Atlanta, Georgia, United States
The Emory Clinic - Emory Healthcare - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Northside Hospital, Inc.
🇺🇸Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Parkview Cancer Institute - Fort Wayne Radiation Oncology Associates
🇺🇸Fort Wayne, Indiana, United States
The University of Kansas Cancer Center
🇺🇸Topeka, Kansas, 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
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
LSU Health Sciences Center, New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Health System
🇺🇸New Orleans, Louisiana, United States
Maine Medical Partners Neurology - Neurosurgery & Spine Associates
🇺🇸South Portland, Maine, United States
John Hopkins School of Medicine
🇺🇸Baltimore, Maryland, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
JFK Neuroscience Institute, HMH JFK University Medical Center
🇺🇸Edison, New Jersey, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Massachusetts Chan Medical School
🇺🇸Worcester, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Missouri - Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Health Midwest Ventures Group, Inc - Sarah Cannon HCA Midwest Brain and Spine
🇺🇸Kansas City, Missouri, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Novant Health Cancer Institute Radiation Oncology
🇺🇸Charlotte, North Carolina, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center - John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Northwell Health System Brain Tumor Center
🇺🇸Lake Success, New York, United States
NYU Langone - Laura & Issac Perimutter Cancer Center
🇺🇸New York, New York, United States
Mount Sinai - Icahn School of Medicine
🇺🇸New York, New York, United States
Vidant Medical Center
🇺🇸Greenville, North Carolina, United States
New York Presbyterian - Columbia University
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of North Carolina Brain Tumor Program - UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, 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 Cincinnati Cancer Institute
🇺🇸Cincinnati, Ohio, United States
The James Cancer Hospital and Solove Research Institute - Arthur G James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny Health Network Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
MUSC Radiation Oncology Brain & Spine Tumor Program
🇺🇸Charleston, South Carolina, United States
SCRI - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
West Cancer Center - Germantown
🇺🇸Germantown, Tennessee, United States
Texas Oncology Midtown - Austin Brain Tumor Center
🇺🇸Austin, Texas, United States
Baylor Charles A. Sammons Cancer Center - Baylor University Medical Center
🇺🇸Dallas, Texas, United States
John Peter Smith Health Network - JPS Cancer Center
🇺🇸Fort Worth, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
UT Health Mischer Neuroscience - Memorial Herman - UT Neurosciences
🇺🇸Houston, Texas, United States
Baylor Scott & White Medical Center
🇺🇸Temple, Texas, United States
The University of Vermont Medical Center - University of Vermont Cancer Center
🇺🇸Burlington, Vermont, United States
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Ishikawa-Ken, Japan
Massey Cancer Center - VCU Medical Center
🇺🇸Richmond, Virginia, United States
UW Medical Center - Alvord Brain Tumor Center
🇺🇸Seattle, Washington, United States
Swedish Health Services
🇺🇸Seattle, Washington, United States
West Virginia University Cancer Institute
🇺🇸Morgantown, West Virginia, United States
Innsbruck University Hospital
🇦🇹Innsbruck, Austria
Kepler University Hospital
🇦🇹Linz, Austria
University Hospital Salzburg
🇦🇹Salzburg, Austria
Hospital Erasme
🇧🇪Brussels, Belgium
University Hospital Liege - Sart Tilman
🇧🇪Liège, Belgium
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Sunnybrook Research Institute - Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
CHUM Centre de Recherche
🇨🇦Montréal, Quebec, Canada
Universite de Sherbrooke - Sherbrooke Centre Hospitalier Universita
🇨🇦Sherbrooke, Quebec, Canada
Masaryk Memorial Cancer Institute
🇨🇿Brno, Czechia
University Hospital Plzeň
🇨🇿Pilsen, Czechia
Na Homolce Hospital
🇨🇿Prague, Czechia
Institut de cancérologie de l'Ouest
🇫🇷Saint Herblain, France
Pierre Wertheimer Hospital
🇫🇷Bron, France
Hôpital la Timone
🇫🇷Marseille, France
University Hospital Nice
🇫🇷Nice, France
Pitié-Salpêtrière University Hospital
🇫🇷Paris, France
University Institute Cancer Toulouse Oncopole
🇫🇷Toulouse, France
Gustave Roussy Institute
🇫🇷Villejuif, France
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, Germany
Rambam Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Center - Ein Kerem
🇮🇱Jerusalem, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Saitama Medical University International Medical Center
🇯🇵Hidaka-shi, Saitama-Ken, Japan
Kyorin University Hospital
🇯🇵Mitaka-shi, Tokyo-To, Japan
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Hokkaido University Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo-To, Japan
Lausanne University Hospital
🇨🇭Lausanne, Switzerland
University Hospital Zurich
🇨🇭Zürich, Switzerland
Clatterbridge Cancer Centre
🇬🇧Liverpool, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom