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EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma

Phase 3
Recruiting
Conditions
Glioblastoma
Interventions
Device: Optune® device
Drug: Placebo
Registration Number
NCT06556563
Lead Sponsor
NovoCure GmbH
Brief Summary

This is a multicenter, two-arm, randomized, double-blind, placebo-controlled study of Optune® (Tumor Treating Fields at 200 kHz) together with maintenance Temozolomide (TMZ) chemotherapy agent and pembrolizumab compared to Optune® together with maintenance TMZ and placebo in newly diagnosed Glioblastoma (GBM) patients. The primary objective of the study is to evaluate the Overall Survival (OS).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
741
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 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment GroupOptune® device-
Treatment GroupPembrolizumab-
Treatment GroupTemozolomide-
Control GroupOptune® device-
Control GroupTemozolomide-
Control GroupPlacebo-
Primary Outcome Measures
NameTimeMethod
Overall survival24 months

Overall survival (OS) is defined as the time from randomization to death due to any cause

Secondary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS) per RANO assessed by investigator24 months

PFS is defined as the time interval, in months, between randomization and the first documented disease progression per RANO assessed by investigator or death due to any cause, whichever occurs first.

Note: RANO = Response Assessment in Neuro-Oncology

Progression-Free Survival (PFS) per mRANO assessed by investigator24 months

PFS is defined as the time interval, in months, between randomization and the first documented disease progression per mRANO assessed by investigator or death due to any cause, whichever occurs first.

Note: mRANO = Modified Radiographic Response Assessment in Neuro-Oncology

Trial Locations

Locations (28)

Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust)

🇬🇧

Cambridge, United Kingdom

University of Southern California

🇺🇸

Los Angeles, California, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

The Christie Hospital

🇬🇧

Manchester, United Kingdom

Royal Marsden

🇬🇧

Sutton, United Kingdom

Hoag Memorial Hospital Presbyterian

🇺🇸

Newport Beach, California, United States

UF Health Neuromedicine

🇺🇸

Gainesville, Florida, United States

Miami Cancer Institute

🇺🇸

Miami, Florida, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Huntsman Cancer Institute, University of Utah

🇺🇸

Salt Lake City, Utah, United States

Institut Claudius Regaud

🇫🇷

Toulouse, France

University of Kentucky Medical Center

🇺🇸

Lexington, Kentucky, United States

UPMC Hillman Cancer Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

John Theurer Cancer Center/ Hackensack Meridian Health

🇺🇸

Hackensack, New Jersey, United States

The Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Inova Schar Cancer Institute

🇺🇸

Fairfax, Virginia, United States

Groupe Hospitalier Pitie - Salpetriere

🇫🇷

Paris, France

Columbia University Irving Medical Center

🇺🇸

New York, New York, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Clinical Trials Organization

🇺🇸

Philadelphia, Pennsylvania, United States

Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Rabin Medical Center- Beilinson Hospital

🇮🇱

Petah tikva, Israel

Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

Stanford Cancer Institute

🇺🇸

Palo Alto, California, United States

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