EF-32 (TRIDENT): An open, randomized registration study of Optune® (TTFields, 200kHz) as an adjunct therapy to radiation therapy and temozolomide for the treatment of newly diagnosed glioblastoma
Résumé de l'étude
We aim to investigate the efficacy and safety of the medical device Optune® in combination with standard radiation therapy and chemotherapy in the treatment of a newly diagnosed glioblastoma multiforme (brain tumor). Current standard medical care includes Optune® as an adjunct therapy for treatment with temozolomide as maintenance therapy after completion of radiation therapy. The goal of the current study is to determine whether early treatment with Optune®, alongside radiation therapy and temozolomide as treatment for newly diagnosed glioblastomas, significantly improves clinical outcomes in patients compared to standard treatment. This study will involve 950 participants aged 18 years and older with a newly diagnosed glioblastoma multiforme, who will receive radiation therapy (RT) in combination with temozolomide (TMZ) after surgery or biopsy, at multiple centers in the USA, Europe, and Israel. The study duration is estimated to be at least 72 months. The duration of the study per patient is estimated to be 24 months.
(BASEC)
Intervention étudiée
Once the investigator has determined that the patient meets all eligibility criteria for the study, they will be randomly assigned (like flipping a coin) to one of the following two groups:
Group 1) Optune® + radiation therapy + temozolomide for a duration of 6 weeks, followed by Optune® + temozolomide until tumor progression. Treatment with Optune can be continued without tumor progression for up to 24 months.
Group 2) Radiation therapy + temozolomide for a duration of 6 weeks followed by Optune® + temozolomide until tumor progression. Treatment with Optune can be continued without tumor progression for up to 24 months. The treatment for patients in Group 2 corresponds to the standard treatment that patients would receive if they were not participating in the study.
The probability of assignment to either group is equal.
Optune® is a portable, battery-powered device that delivers electric fields, known as tumor treatment fields (TTFields), at a specific frequency to the patient using isolated electrodes.
TTF field therapy generates electric forces intended to destroy cancer cells in the brain. The device and battery are carried in a shoulder or side bag.
TTFields is a treatment type for cancer tumors. Laboratory studies have shown the potential effect of slowing tumor growth without causing significant side effects. Large clinical studies have confirmed the safety and efficacy of Optune® in patients with recurrent and newly diagnosed glioblastoma.
Treatment with Optune® will take place in the clinic's outpatient department as well as at the patient's home, as the treatment is to be administered over a period of 18 hours, spread throughout the day. During this appointment, patients will be instructed on the operation of the device. Patients will wear four electrically isolated electrodes on their head during the duration of the device application. For the placement of the electrodes, the patient's head must be shaved. During the study duration, patients should use Optune® for at least 18 hours per day.
Each treatment unit with Optune® consists of one month of continuous use. Multiple treatment units will be offered as long as the brain tumor does not recur or for a period of 24 months, whichever comes first. In the event of tumor recurrence, the patient may continue treatment with Optune® until a new recurrence occurs. If a recurrence occurs twice, the patient must discontinue the use of Optune®.
Patient participation will last up to 24 months. During this time, 17 study visits will be required. Patients must visit the study center every 4 weeks during the first 6 months of study participation and then every 8 weeks until participation ends.
At follow-up visits, the patient will be asked about their general health status and any medications they are taking, a physical and neurological examination will be performed, and blood samples will be taken. Additionally, every 12 weeks, a contrast MRI of the head will be performed and the patient will be asked to complete a health questionnaire.
The patient must attend another appointment, 30 days +/- 7 days after the last Optune® treatment, or upon occurrence of the second recurrence at the clinic's outpatient department.
After the conclusion of the study with Optune®, the patient will be contacted by phone once a month to answer basic questions regarding their health status. Another visit to the clinic is not necessary unless the doctor orders it as part of routine care.
(BASEC)
Maladie en cours d'investigation
The study will investigate a newly diagnosed glioblastoma multiforme (brain tumor).
(BASEC)
1. Histologically confirmed diagnosis of a newly diagnosed glioblastoma multiforme (brain tumor) according to WHO classification criteria 2. Age ≥ 18 years 3. Life expectancy ≥ 3 months minimum (BASEC)
Critères d'exclusion
1. Progressive disease (per investigator assessment) 2. Infratentorial or leptomeningeal disease 3. Implantable pacemaker, defibrillator, deep brain stimulation, other implantable devices in the brain, or document clinically significant arrhythmias. (BASEC)
Lieu de l’étude
Zurich
(BASEC)
Sponsor
Novocure GmbH, Neuhofstrasse 21, CH-6340 Baar, Switzerland
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Patrick Roth
+41 (0)44 255 5511
patrick.roth@clutterusz.chUniversity Hospital Zürich
(BASEC)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale de Zurich
(BASEC)
Date d'approbation du comité d'éthique
27.04.2021
(BASEC)
Identifiant de l'essai ICTRP
NCT04471844 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
EF-32 (Trident): A pivotal randomized, open-label study of Optune® (TTFields, 200khz) concomitant with radiation therapy and temozolomide for the treatment of newly diagnosed glioblastoma (BASEC)
Titre académique
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 (ICTRP)
Titre public
Pivotal, Randomized, Open-label Study of Optune (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM (ICTRP)
Maladie en cours d'investigation
Glioblastoma Multiforme (ICTRP)
Intervention étudiée
Device: Optune (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
*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 -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/L)
2. Neutropenia (absolute neutrophil count < 1.5 x 103/L)
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 mol/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 (ICTRP)
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Critères d'évaluation principaux et secondaires
Overall Survival (OS) (ICTRP)
Progression Free Survival (PFS);1- and 2-year survival rates;Overall Radiological response (ORR);Next progression-free survival (PFS2);Progression-free survival at 6 (PFS6) and 12 months (PFS12);Severity and frequency of adverse events;Quality of Life EORTC Questionnaire;The NANO scale (ICTRP)
Date d'enregistrement
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Inclusion du premier participant
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Sponsors secondaires
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Contacts supplémentaires
Doron Manzur, MD, clinicaltrials@novocure.com, +1 603 206 2337 (ICTRP)
ID secondaires
TRIDENT EF-32 (ICTRP)
Résultats-Données individuelles des participants
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Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT04471844 (ICTRP)
Résultats de l'essai
Résumé des résultats
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Lien vers les résultats dans le registre primaire
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