Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM (EF-32)

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

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Device: Optune®

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 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.

• Study Type: Interventional
• Enrollment (Actual): 981
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Innsbruck
    • Innsbruck, Innsbruck, Austria, 6020
      • Innsbruck University Hospital
  • Linz
    • Linz, Linz, Austria, 4020
      • Kepler University Hospital
  • Salzburg
    • Salzburg, Salzburg, Austria, 5020
      • University Hospital Salzburg
• Belgium
  • Brussels, Belgium, 1070
    • Hospital Erasme
  • Liège, Belgium, B35, 4000
    • University Hospital Liege - Sart Tilman
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer - Vancouver
  • Nova Scotia
    • Sydney, Nova Scotia, Canada, B1P 1P3
      • Nova Scotia Health Authority
  • Ontario
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada
      • Sunnybrook Research Institute - Odette Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X1R9
      • CHUM Centre de Recherche
    • Sherbrooke, Quebec, Canada
      • Universite de Sherbrooke - Sherbrooke Centre Hospitalier Universita
• Czechia
  • Brno
    • Brno, Brno, Czechia, 656 53
      • Masaryk Memorial Cancer Institute
  • Pilsen
    • Pilsen, Pilsen, Czechia, 305 99
      • University Hospital Plzen
  • Prague
    • Prague, Prague, Czechia, 150 30
      • Na Homolce Hospital
• France
  • Angers, France, 49055
    • Institut de cancerologie de l'ouest
  • Bron, France, 69677
    • Pierre Wertheimer Hospital
  • Marseille, France, 13305
    • Hôpital la Timone
  • Nice, France, 06000
    • University Hospital Nice
  • Paris, France, 75013
    • Pitié-Salpêtrière University Hospital
  • Saint-Herblain, France, 44800
    • Institut de cancerologie de l'ouest
  • Toulouse, France, 31059
    • University Institute Cancer Toulouse Oncopole
  • Villejuif, France, 94805
    • Gustave Roussy Institute
• Germany
  • Berlin, Germany, 13353
    • Charité Campus Virchow Clinic
  • Essen, Germany, 45147
    • University Hospital Essen
  • Freiburg im Breisgau, Germany, 79106
    • University Medical Center Freiburg
  • Leipzig, Germany, 04103
    • University Hospital Leipzig
  • Munich, Germany, 81675
    • Rechts der Isar Hospital
  • Tübingen, Germany, 72076
    • University Hospital Tübingen
• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center - Ein Kerem
  • Haifa District
    • Haifa, Haifa District, Israel, 3109601
      • Rambam Medical Center
  • Petah Tikva
    • Petah Tikva, Petah Tikva, Israel, 49100
      • Rabin Medical Center
  • Ramat Gan
    • Ramat Gan, Ramat Gan, Israel, 52621
      • Sheba Medical Center
  • Tel Aviv
    • Tel Aviv, Tel Aviv, Israel, 64239
      • Tel Aviv Sourasky Medical Center
• Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital
  • Saitama
    • Hidaka-shi, Saitama, Japan, 350-1298
      • Saitama Medical University International Medical Center
  • Tokyo-To
    • Mitaka-shi, Tokyo-To, Japan, 181-8611
      • Kyorin University Hospital
    • Shinjuku-ku, Tokyo-To, Japan, 162-8666
      • Tokyo Women's Medical University Hospital
• Switzerland
  • Lausanne, Switzerland, CH-1011
    • Lausanne University Hospital
  • Zurich, Switzerland, 8091
    • University Hospital Zurich
• United Kingdom
  • Liverpool, United Kingdom, L7 8YA
    • Clatterbridge Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
  • Preston, United Kingdom, PR29HT
    • Royal Preston Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Grandview Cancer Center
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic- Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center
  • Arkansas
    • Fayetteville, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Burbank, California, United States, 91505
      • Providence St. Joseph Medical Center and The Roy and Patricia Disney Family Cancer Center
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Fullerton, California, United States, 92835
      • TRIO - St. Jude Heritage Healthcare/St. Jude Medical Center
    • La Jolla, California, United States, 92093
      • University of California at San Diego - Moores Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars - Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Norris Comprehensive Cancer Center at USC
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital - Hoag Cancer Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital of Orange
    • Orange, California, United States, 92868
      • University of California - Irvine/UCI Medical Center
    • Palo Alto, California, United States, 94303
      • Stanford University Cancer Institute
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital - X-Ray Medical Group Radiation Oncology
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute at St. John's Health Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center Anschutz
    • Englewood, Colorado, United States, 80113
      • HCA Research Institute - Blue Sky Neurology - Denver
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Healthcare Medical Group - Hartford Hospital The Gray Cancer Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute, Marcus Neuroscience Institute
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jacksonville, Florida, United States, 32207
      • Baptist Health - Jacksonville
    • Orlando, Florida, United States, 32804
      • AdventHealth
    • Orlando, Florida, United States, 32806
      • Orlando Health UF Health Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc.
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare Brain Tumor Center
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic - Emory Healthcare - Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60617
      • University of Chicago
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Cancer Institute - Fort Wayne Radiation Oncology Associates
  • Kansas
    • Topeka, Kansas, United States, 66606
      • The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Cancer Institute
    • Louisville, Kentucky, United States, 40202
      • University of Louisville - James Graham Brown Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70810
      • Mary Bird Cancer Center Neuromedical Center
    • New Orleans, Louisiana, United States, 70072
      • LSU Health Sciences Center, New Orleans
    • New Orleans, Louisiana, United States, 70121-2429
      • Ochsner Health System
  • Maine
    • South Portland, Maine, United States, 04106
      • Maine Medical Partners Neurology - Neurosurgery & Spine Associates
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Chan Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital - Givens Brain Tumor Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel Cancer Center
    • Kansas City, Missouri, United States, 64132
      • Health Midwest Ventures Group, Inc - Sarah Cannon HCA Midwest Brain and Spine
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Edison, New Jersey, United States, 08820
      • JFK Neuroscience Institute, HMH JFK University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center - John Theurer Cancer Center
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health System Brain Tumor Center
    • New York, New York, United States, 10029
      • Mount Sinai - Icahn School of Medicine
    • New York, New York, United States, 10016
      • NYU Langone - Laura & Issac Perimutter Cancer Center
    • New York, New York, United States, 10032
      • New York Presbyterian - Columbia University
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Brain Tumor Program - UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute Radiation Oncology
    • Greenville, North Carolina, United States, 27834
      • Vidant Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Medical Center-Novant Health
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Institute
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital and Solove Research Institute - Arthur G James Cancer Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Neuroscience Center, Philadelphia - University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Cancer Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Radiation Oncology Brain & Spine Tumor Program
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • SCRI - Tennessee Oncology
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center - Germantown
    • Nashville, Tennessee, United States, 37203
      • SCRI - Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology Midtown - Austin Brain Tumor Center
    • Dallas, Texas, United States, 75246
      • Baylor Charles A. Sammons Cancer Center - Baylor University Medical Center
    • Fort Worth, Texas, United States, 76104
      • John Peter Smith Health Network - JPS Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • UT Health Mischer Neuroscience - Memorial Herman - UT Neurosciences
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center - University of Vermont Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Massey Cancer Center - VCU Medical Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Health Services
    • Seattle, Washington, United States, 98109
      • UW Medical Center - Alvord Brain Tumor Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

*Age Limits - 18 years or older outside of the US, 22 years or older within the US.

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.

15. Standard TTFields exclusion criteria include

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Survival will be measured from the time of randomization until date patient is alive.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Next progression-free survival (PFS2)	PFS2 will be measured from the time of randomization to second tumor progression.	5 years
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
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
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
Progression Free Survival (PFS)	PFS will be measured from the date of randomization to the date of progression based on the 2010 RANO Criteria.	5 years
Overall Radiological response (ORR)	The analyses will be performed based on the 2010 RANO criteria, and comparison between the rates of response.	5 years
The NANO scale	The Neurological assessment in Neuro-Oncology will be assessed using the NANO scale questionnaire and per the 2010 RANO criteria.	5 years

Collaborators and Investigators

• Sponsor: NovoCure Ltd.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): February 19, 2026
• Study Completion (Actual): February 19, 2026

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: July 13, 2020
• First Posted (Actual): July 15, 2020

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: GBM
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: TRIDENT EF-32

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No