Study of Optune® (TTFields, 200khz) Concomitant with Radiation Therapy and Temozolomide for the Treatment of Newly Diagnosed Glioblastoma
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
Clinical Trial Information
Trial Contact: Manchola-Orozco, Carolina; Walton, Sherri
IRB No: W20.119.07
Protocol Abbrev: TRIDENT/EF-32
Principal Investigator: Nicholas G. Avgeropoulos, MD
Phase: Device: Significant Risk
Age Group: Adult
Secondary Protocol No: EF-32
Treatment: Each of these treatments is briefly described below: 1. Surgical resection - Treatment of patients with GBM usually consists of tumor resection (to the extent safely feasible) or diagnostic biopsy. 2. Radiotherapy (RT) - Post-surgical RT improves survival, though even with maximal treatment, survival after RT alone is still limited to about one year3. 3. Temozolomide (TMZ) – Concomitant TMZ chemotherapy during RT and adjuvant (maintenance) TMZ for 6 cycles has been shown to significantly improve survival (HR 0.63)3. This combined modality treatment is considered the standard of care. According to the TMZ (Temodar®, Temodal®) package insert adjuvant TMZ treatment delays disease progression (from 5 to 6.9 months) and improves overall survival (from 12.1 to 14.6 months)3. 4. GLIADEL™ Wafers in combination with surgical resection – Gliadel™ Wafers deliver carmustine (BCNU) directly to the bed of the resected tumor. Gliadel has been approved for GBM after surgical resection, based on trials performed before TMZ therapy was established7. The package insert indicates that for newly diagnosed GBM, Gliadel™ increased median overall survival from 11.6 to 13.9 months compared to placebo. 5. TTFields - Large-scale, phase III clinical studies have validated the safety and efficacy of TTFields in patients with recurrent and newly diagnosed glioblastoma6,8. Accordingly, TTFields (Optune®) are now FDA-approved and have obtained a CE mark in Europe for use in newly diagnosed and recurrent GBM. 6. Lomustine-TMZ as maintenance therapy might improve survival in newly diagnosed patients compared to maintenance TMZ alone, as suggested by an open-label phase 3 trial in 141 patients, which demonstrated a HR of 0.6 (95% CI 0.35-1.03, p=0.0492) for the combined treatment9.
Therapies Involved: Chemotherapy;Radiation
ClinicalTrials.gov ID: PENDING
To determine if TTFields treatment at 200 kHz to the brain concomitantly with RT and TMZ in the treatment of GBM patients prolongs the overall survival of patients, compared to RT and TMZ
treatments followed by TTFields and maintenance TMZ.
1. Histologically confirmed diagnosis of GBM according to WHO classification criteria.
2. Age ≥ 18 years
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
10. Concomitant RT with TMZ treatment planned to start no later than 8 weeks from surgery
All individuals meeting any of the following exclusion criteria will be excluded from study
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:
a. Thrombocytopenia (platelet count < 100 x 103/μL)
b. Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
c. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
d. Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
e. Total bilirubin > 1.5 x upper limit of normal
f. Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 μmol/l)
g. 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. Any other cytotoxic or biologic anti-tumor therapy received prior to enrollment will be
10. Admitted to an institution by administrative or court order.
11. Known allergies to medical adhesives or hydrogel