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
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 981
- 试验地点
- 260
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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.
详细描述
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®.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of GBM according to WHO 2016 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 randomization
- •Is able to have MRI with contrast of the brain
排除标准
- •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.
- •Additional malignancies that are progressing or required active treatment in the last two years.
- •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 put the participant at risk according to the investigator.
- •Standard TTFields exclusion criteria include
- •Active implanted medical devices
- •Bullet fragments
- •Skull defects
研究组 & 干预措施
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.
干预措施: Optune® (Device)
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.
干预措施: Optune® (Device)
结局指标
主要结局
Overall Survival (OS)
时间窗: 5 years
Survival will be measured from the time of randomization until date patient is alive.
次要结局
- Progression Free Survival (PFS)(5 years)
- 1- and 2-year survival rates(5 years)
- Overall Radiological response (ORR)(5 years)
- Next progression-free survival (PFS2)(5 years)
- Progression-free survival at 6 (PFS6) and 12 months (PFS12)(5 years)
- Severity and frequency of adverse events(5 years)
- Quality of Life EORTC Questionnaire(5 years)
- The NANO scale(5 years)
- Progression Free Survival (PFS)(5 years)
- 1- and 2-year survival rates(5 years)
- Overall Radiological response (ORR)(5 years)
- Next progression-free survival (PFS2)(5 years)
- Progression-free survival at 6 (PFS6) and 12 months (PFS12)(5 years)
- Severity and frequency of adverse events(5 years)
- Quality of Life EORTC Questionnaire(5 years)
- The NANO scale(5 years)