A study on patients with newly diagnosed glioblastoma to evaluate the efficacy and safety of Optune® (tumor treating fields, TTFields) in combination with temozolomide and pembrolizumab compared to Optune® (TTFields) in combination with temozolomide and placebo.
Descrizione riassuntiva dello studio
The currently approved treatment for ndGBM includes the addition of maintenance chemotherapy with temozolomide (TMZ) via Optune® after completion of radiotherapy and chemotherapy (RT + TMZ). This study aims to compare the effects of pembrolizumab in combination with Optune® and TMZ maintenance therapy versus placebo in combination with Optune® and TMZ maintenance therapy in treating patients with ndGBM. Optune® is a portable device consisting of the following components: a device to generate electric fields, 4 transducer arrays, and a power source. Transducer arrays consist of a medical cap with electrically isolated electrodes placed on the scalp where your primary tumor is located, delivering TTFields. TTFields is a treatment method for cancerous tumors. Laboratory studies have shown that this method can slow tumor growth without causing significant side effects. Extensive clinical studies have confirmed the safety and efficacy of Optune® in patients with recurrent and newly diagnosed GBM. TTFields may potentially enhance the immune response by sensitizing the tumor to immune checkpoint inhibitors such as pembrolizumab. Pembrolizumab is known as a checkpoint inhibitor that enhances the body's immune response against cancer cells. Pembrolizumab is approved in Switzerland as a medication for the treatment of various tumor types, but not for the treatment of ndGBM.
(BASEC)
Intervento studiato
When standard radiotherapy and chemotherapy (RT + TMZ) is completed and the investigator has determined that all eligibility criteria for study participation are met, participants will be randomly assigned to one of two groups:
a. Optune® + TMZ + pembrolizumab.
b. Optune® + TMZ + placebo.
The likelihood of being assigned to the experimental group receiving Optune® + TMZ + pembrolizumab is twice as high. This study will be conducted as a double-blind study. This means that neither the treating physician nor the study participants know which treatment group they are assigned to. The placebo contains no active ingredient and is administered in the same way as pembrolizumab.
Pembrolizumab or placebo will be administered every 3 weeks at a dose of 200 mg. Pembrolizumab or placebo will be administered intravenously at the study center (infusion into a vein). Additionally, maintenance therapy with TMZ (temozolomide) will be administered during the treatment period.
At the start of the study, a Novocure Device Support Specialist (DSS) will instruct study participants on the proper use of Optune®. The Optune® treatment will be continuous for at least 18 hours per day (monthly average). Study participants may take breaks for personal needs (e.g., showering, array change) as long as treatment is provided for 18 hours per day (monthly average).
(BASEC)
Malattie studiate
Newly diagnosed glioblastoma multiforme (ndGBM, brain tumor)
(BASEC)
• Newly diagnosed GBM • Recovery after maximal debulking surgery (all patients with complete resection, partial resection, and only a biopsy are acceptable) • Completed standard adjuvant radiotherapy and chemotherapy with RT and concurrent TMZ chemotherapy (BASEC)
Criteri di esclusione
with an active ingredient targeting another stimulating or co-inhibitory T-cell receptor • Ongoing need for > 2 mg dexamethasone (or an equivalent active ingredient) due to an intracranial mass effect • An additional malignancy that is progressing or required active treatment in the last 3 years (BASEC)
Luogo dello studio
Basilea, Losanna, Zurigo
(BASEC)
Sponsor
Novocure GmbH, Baar, Switzerland IQVIA AG, Branch Basel, Basel, Switzerland
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Prof. Dr. med. Michael Weller
+41 44 255 55 00
michael.weller@clutterusz.chUniversitätsspital Zürich, Klinik für Neurologie, Frauenklinikstrasse 26, 8091 Zürich
(BASEC)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
20.12.2024
(BASEC)
ID di studio ICTRP
NCT06556563 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Optune® (TTFields, 200 kHz) Concomitant with Maintenance Temozolomide and Pembrolizumab Versus Optune® Concomitant with Maintenance Temozolomide and Placebo for the Treatment of Newly Diagnosed Glioblastoma (EF-41/KEYNOTE D58) (BASEC)
Titolo accademico
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Optune (TTFields, 200 kHz) Concomitant With Maintenance Temozolomide and Pembrolizumab Versus Optune Concomitant With Maintenance Temozolomide and Placebo for the Treatment of Newly Diagnosed Glioblastoma (EF-41/KEYNOTE D58). (ICTRP)
Titolo pubblico
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma (ICTRP)
Malattie studiate
Glioblastoma (ICTRP)
Intervento studiato
Device: Optune deviceDrug: TemozolomideDrug: PembrolizumabDrug: Placebo (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Criteri di inclusione/esclusione
Inclusion Criteria:
1. The participant (or legally acceptable representative) has provided documented
informed consent for the study.
2. Be = 18 years of age on day of providing informed consent.
3. Participant with new diagnosis of GBM according to World Health Organization (WHO)
2021 Classification.
4. Recovered from maximal debulking surgery (gross total resection, partial resection
and biopsy-only patients are all acceptable), Gliadel wafers placement at the time
of surgical resection is not allowed.
5. Have completed standard adjuvant chemoradiotherapy of radiotherapy (RT) according to
local practice (56-64 Gy), and concomitant TMZ chemotherapy.
6. Amenable to treatment with Optune concomitant with maintenance TMZ (150-200 mg/m^2
daily x 5, Q28 days).
7. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
assessed within 7 days before randomization.
8. Stable or decreasing dose of corticosteroids (dexamethasone = 2mg or equivalent) for
the last 7 days prior to randomization, if applicable.
Exclusion Criteria:
1. Has received prior therapy with an anti-Programmed Cell Death 1 (PD-1), anti-
Programmed Cell Death-Ligand 1(PD-L1), or anti Programmed Cell Death-Ligand 2
(PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory
T-cell receptor (e.g.Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4), OX 40,
CD137).
2. Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial
mass effect.
3. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to randomization.
4. Received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines are allowed.
5. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first study
treatment.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study medication.
Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
7. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
8. Early progressive disease after the end of TMZ/RT. If pseudo progression is
suspected, additional imaging studies should be performed to rule out true
progression.
9. Infratentorial or leptomeningeal disease. (ICTRP)
non disponibile
Endpoint primari e secondari
Overall survival (ICTRP)
Progression-Free Survival (PFS) per RANO 2.0 assessed by investigator;Progression-Free Survival (PFS) per RANO 2.0 assessed by investigator (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
Merck Sharp & Dohme LLC (ICTRP)
Contatti aggiuntivi
Uz Stammberger, clinicaltrials@novocure.com, 1-877-678-8611 (ICTRP)
ID secondari
2024-513550-30-00, EF-41 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT06556563 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile