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

Sponsor

NovoCure GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04471844

Collaborator

(none)

950

Enrollment

119

Locations

Arms

67.7

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	Device: Optune®	N/A

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:

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.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

950 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomly assigned equally to one of two groups: a. 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. 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®.Randomly assigned equally to one of two groups: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. 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®.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 8, 2020

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

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 or 24 months.	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.
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.	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.

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 or 24 months.

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.

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.

Device: Optune®

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [5 years]
Survival will be measured from the time of randomization until date patient is alive.

Secondary Outcome Measures

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.
Overall Radiological response (ORR) [5 years]
The analyses will be performed based on the RANO criteria, and comparison between the rates of response.
Next progression-free survival (PFS2) [5 years]
PFS2 will be measured from the time of randomization to second tumor progression.
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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 registration
Is able to have MRI with contrast of the brain

Exclusion Criteria:

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.
Any other cytotoxic or biologic anti-tumor therapy received prior to enrollment will be considered exclusion.
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 risk the patient according to the investigator
Standard TTFields exclusion criteria include
Active implanted medical devices
Bullet fragments
Skull defects

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Grandview Cancer Center	Birmingham	Alabama	United States	35243
2	Mayo Clinic- Arizona	Phoenix	Arizona	United States	85054
3	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
4	Highlands Oncology Group	Fayetteville	Arkansas	United States	72762
5	City of Hope National Medical Center	Duarte	California	United States	91010
6	TRIO - St. Jude Heritage Healthcare/St. Jude Medical Center	Fullerton	California	United States	92835
7	University of California at San Diego - Moores Cancer Center	La Jolla	California	United States	92093
8	Norris Comprehensive Cancer Center at USC	Los Angeles	California	United States	90033
9	Cedars - Sinai Medical Center	Los Angeles	California	United States	90266
10	Providence St. Joseph Medical Center and The Roy and Patricia Disney Family Cancer Center	Los Angeles	California	United States	91505
11	Hoag Memorial Hospital - Hoag Cancer Center	Newport Beach	California	United States	92663
12	St. Joseph Hospital of Orange	Orange	California	United States	92868
13	St. Joseph's Hospital	Orange	California	United States	92868
14	University of California - Irvine/UCI Medical Center	Orange	California	United States	92868
15	Stanford University Cancer Institute	Palo Alto	California	United States	94303
16	Sharp Memorial Hospital - X-Ray Medical Group Radiation Oncology	San Diego	California	United States	92123
17	University of California San Francisco Medical Center	San Francisco	California	United States	94143
18	John Wayne Cancer Institute at St. John's Health Center	Santa Monica	California	United States	90404
19	Stanford Cancer Institute	Stanford	California	United States	94305
20	University of Colorado Cancer Center Anschutz	Aurora	Colorado	United States	80045
21	HCA Research Institute - Blue Sky Neurology - Denver	Englewood	Colorado	United States	80113
22	Hartford Healthcare Medical Group - Hartford Hospital The Gray Cancer Center	New London	Connecticut	United States	06320
23	Lynn Cancer Institute, Marcus Neuroscience Institute	Boca Raton	Florida	United States	33486
24	Baptist Health - Jacksonville	Jacksonville	Florida	United States	32207
25	Mayo Clinic	Jacksonville	Florida	United States	32224
26	AdventHealth	Orlando	Florida	United States	32804
27	Orlando Health UF Health Cancer Center	Orlando	Florida	United States	32806
28	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida	United States	33612
29	Piedmont Healthcare Brain Tumor Center	Atlanta	Georgia	United States	30309
30	The Emory Clinic - Emory Healthcare - Winship Cancer Institute	Atlanta	Georgia	United States	30322
31	Rush University Medical Center	Chicago	Illinois	United States	60612
32	Parkview Cancer Institute - Fort Wayne Radiation Oncology Associates	Fort Wayne	Indiana	United States	46845
33	The University of Kansas Cancer Center	Overland Park	Kansas	United States	66210
34	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
35	Norton Cancer Institute	Louisville	Kentucky	United States	40241
36	NeuroMedical Center - Mary Bird Cancer Center	Baton Rouge	Louisiana	United States	70810
37	LSU Health Sciences Center, New Orleans	New Orleans	Louisiana	United States	70072
38	Ochsner Health System	New Orleans	Louisiana	United States	70121-2429
39	Maine Medical Partners Neurology - Neurosurgery & Spine Associates	South Portland	Maine	United States	04106
40	John Hopkins School of Medicine	Baltimore	Maryland	United States	21287
41	Tufts Medical Center	Boston	Massachusetts	United States	02111
42	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
43	Abbott Northwestern Hospital - Givens Brain Tumor Center	Minneapolis	Minnesota	United States	55407
44	University of Minnesota Health Clinics and Surgery Center	Minneapolis	Minnesota	United States	55455
45	University of Missouri - Ellis Fischel Cancer Center	Columbia	Missouri	United States	65212
46	Health Midwest Ventures Group, Inc - Sarah Cannon HCA Midwest Brain and Spine	Kansas City	Missouri	United States	64132
47	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
48	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
49	JFK Neuroscience Institute, HMH JFK University Medical Center	Edison	New Jersey	United States	08820
50	Hackensack University Medical Center - John Theurer Cancer Center	Hackensack	New Jersey	United States	07601
51	Northwell Health System Brain Tumor Center	Lake Success	New York	United States	11042
52	NYU Langone - Laura & Issac Perimutter Cancer Center	New York	New York	United States	10016
53	Mount Sinai - Icahn School of Medicine	New York	New York	United States	10029
54	New York Presbyterian - Columbia University	New York	New York	United States	10032
55	University of Rochester Medical Center	Rochester	New York	United States	14642
56	University of North Carolina Brain Tumor Program - UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
57	Novant Health Medical Center Huntersville	Charlotte	North Carolina	United States	28078
58	Vidant Medical Center	Greenville	North Carolina	United States	27834
59	Forsyth Medical Center-Novant Health	Winston-Salem	North Carolina	United States	27103
60	Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157
61	University of Cincinnati Cancer Institute	Cincinnati	Ohio	United States	45219
62	The James Cancer Hospital and Solove Research Institute - Arthur G James Cancer Hospital	Columbus	Ohio	United States	43210
63	Oregon Health & Science University	Portland	Oregon	United States	97339
64	Geisinger Health System	Danville	Pennsylvania	United States	17822
65	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
66	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
67	Allegheny Health Network	Pittsburgh	Pennsylvania	United States	15061
68	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
69	Rhode Island Hospital	Providence	Rhode Island	United States	02903
70	MUSC Radiation Oncology Brain & Spine Tumor Program	Charleston	South Carolina	United States	29425
71	SCRI - Tennessee Oncology	Chattanooga	Tennessee	United States	37404
72	West Cancer Center - Germantown	Germantown	Tennessee	United States	38138
73	SCRI - Tennessee Oncology	Nashville	Tennessee	United States	37203
74	Texas Oncology Midtown - Austin Brain Tumor Center	Austin	Texas	United States	78705
75	Baylor Charles A. Sammons Cancer Center - Baylor University Medical Center	Dallas	Texas	United States	75246
76	John Peter Smith Health Network - JPS Cancer Center	Fort Worth	Texas	United States	76104
77	Houston Methodist Hospital	Houston	Texas	United States	77030
78	UT Health Mischer Neuroscience - Memorial Herman - UT Neurosciences	Houston	Texas	United States	77030
79	San Antonio Cancer Institute	San Antonio	Texas	United States	78229
80	Baylor Scott & White Medical Center	Temple	Texas	United States	76508
81	The University of Vermont Medical Center - University of Vermont Cancer Center	Burlington	Vermont	United States	05401
82	Massey Cancer Center - VCU Medical Center	Richmond	Virginia	United States	23298
83	Swedish Health Services	Seattle	Washington	United States	98109
84	UW Medical Center - Alvord Brain Tumor Center	Seattle	Washington	United States	98109
85	West Virginia University Cancer Institute	Morgantown	West Virginia	United States	26506
86	Innsbruck University Hospital	Innsbruck		Austria	6020
87	Kepler University Hospital	Linz		Austria	4020
88	University Hospital Salzburg	Salzburg		Austria	5020
89	Hospital Erasme	Brussels		Belgium	1070
90	University Hospital Liege - Sart Tilman	Liège		Belgium	B35, 4000
91	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada
92	Princess Margaret Cancer Centre	Toronto	Ontario	Canada
93	Sunnybrook Research Institute - Odette Cancer Centre	Toronto	Ontario	Canada
94	CHUM Centre de Recherche	Montréal	Quebec	Canada
95	Universite de Sherbrooke - Sherbrooke Centre Hospitalier Universita	Sherbrooke	Quebec	Canada
96	Masaryk Memorial Cancer Institute	Brno		Czechia	656 53
97	University Hospital Plzeň	Pilsen		Czechia	305 99
98	Na Homolce Hospital	Prague		Czechia	150 30
99	Institut de cancérologie de l'Ouest	Angers		France	49055
100	Pierre Wertheimer Hospital	Bron		France	69677
101	Hôpital la Timone	Marseille		France	13305
102	University Hospital Nice	Nice		France	06000
103	Pitié-Salpêtrière University Hospital	Paris		France	75013
104	Institut de cancérologie de l'Ouest	Saint Herblain		France	44800
105	University Institute Cancer Toulouse Oncopole	Toulouse		France	31059
106	Gustave Roussy Institute	Villejuif		France	94805
107	Charité Campus Virchow Clinic	Berlin		Germany	13353
108	University Hospital Essen	Essen		Germany	45147
109	University Medical Center Freiburg	Freiburg		Germany	79106
110	University Hospital Leipzig	Leipzig		Germany	04103
111	Rechts der Isar Hospital	Munich		Germany	81675
112	University Hospital Tübingen	Tübingen		Germany	72076
113	Rambam Medical Center	Haifa		Israel	3109601
114	Hadassah Medical Center - Ein Kerem	Jerusalem		Israel	9112001
115	Rabin Medical Center	Petah Tikva		Israel	49100
116	Sheba Medical Center	Ramat Gan		Israel	52621
117	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
118	Lausanne University Hospital	Lausanne		Switzerland	CH-1011
119	University Hospital Zurich	Zürich		Switzerland	8091

Sponsors and Collaborators

NovoCure GmbH

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

NovoCure GmbH

ClinicalTrials.gov Identifier:

NCT04471844

Other Study ID Numbers:

TRIDENT EF-32

First Posted:

Jul 15, 2020

Last Update Posted:

Jul 13, 2022

Last Verified:

Jul 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Keywords provided by NovoCure GmbH

GBM

Additional relevant MeSH terms:

Glioblastoma

Study Results

No Results Posted as of Jul 13, 2022