A Phase II Trial of Tumor Treating Fields (TTFields) Concomitant With Radiosurgery for the Treatment of Recurrent, Bevacizumab-naïve Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- 1-year survival rate
研究概览
简要总结
All patients will receive TTFields therapy and additionally Stereotactic Radiosurgery . Radiosurgery will be based on MRI and FET-PET or MRI alone. Addition of FET-PET will be preferred option.
详细描述
Almost all GBM patients experience recurrent disease. Stereotactic radiosurgery (SRS),at recurrence, has limitations due to the invasive nature of glioblastoma. TTFields may decrease the tumor aggressiveness outside the target area potentially by multiple pathways, including immunogenic cell death and DNA repair inhibition sensitizing to radiation. We hypothesize that combined SRS and TTFields will be complementary, improving outcomes with minimal toxicity.
In this open-label, phase II trial 40 participants with recurrence will be treated with SRS and TTFields, starting in 2020. Recurrence will be defined on FET-PET or MRI using RANO criteria.
All patients will begin treatment within 14 days from baseline imaging evaluation and at maximum 42 days from screening.
The attempt to obtain the Methyl-guanine methyl-transferase (MGMT) gene promoter methylation and IDH1 and IDH2 mutation from primary tumor are made during the study whenever not defined before entering to the study.
TTFields treatment will be initiated as in clinical routine at patients home. Admission to hospital will not be necessary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patient's written informed consent (IC) obtained at the latest the day after planning MRI;
- •Legal capacity: patient can understand the nature, significance, and consequences of the study;
- •Age ≥18 years (no upper age limit);
- •Karnofsky Performance Score (KPS) ≥ 70;
- •Recurrence of GBM (WHO grade IV) based on RANO criteria or GBM after subtotal resection of recurrence with macroscopic residual tumor;
- •Histological confirmation of GBM at initial or secondary diagnosis;
- •Previous radiotherapy of glioma with a total dose of 59.4 - 60 Gy (single dose 1.8 - 2.0 Gy) and chemotherapy with temozolomide;
- •At least 6 months between the end of the first course of radiotherapy and radiosurgery;
- •Recurrent tumor visible on FET-PET and/or T1Gd-MRI, with the maximum diameter up to 5 cm by either technique (in case of multifocal tumors, the sum of all diameters must be 5 cm on FET-PET and T1Gd-MRI);
- •Start of TTFields before radiosurgery;
- •Disease free from other cancers for ≥ 5 years;
- •Adequate haematologic, renal and hepatic function (absolute neutrophil count ⩾1000/mm3; haemoglobin ⩾100 g/L platelet count, ⩾100,000/mm3; serum creatinine level ⩽1.7 mg/dL (<150 μmol/L); total serum bilirubin level ⩽ the upper limit of normal and liver-function values, <3 times the upper limit of normal);
排除标准
- •Recent (≤ 4 weeks before IC) histological result showing no tumor recurrence;
- •Previous treatment of GBM with bevacizumab;
- •Chemotherapy or molecular targeted therapies planned before diagnosis of further tumor progression after study intervention
- •Simultaneous participation in other interventional trials which could interfere with this trial and/or participation in a clinical trial within the last thirty days before the start of this study and/or previous participation (randomization) in this study;
- •Pregnancy, nursing, or patient not willing to prevent a pregnancy during treatment;
- •Known or persistent abuse of medication, drugs or alcohol;
- •Known allergy against the MRI contrast agent gadolinium or the PET tracer 18F-FET or against any of the components;
- •Evidence of increased intracranial pressure (midline shift >5 mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness);
- •Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
- •Gross total resection of recurrence confirmed with postoperative MRI and negative FET-PET result
- •Other malignancies ,except for non-melanomatous skin cancers, or carcinoma in-situ of uterus, cervix or bladder
结局指标
主要结局
1-year survival rate
时间窗: 12 Months
Survival will be measured from date of enrollment until date of death
次要结局
- Progression free survival (PFS)(12 moths)
- Radiation necrosis range(12 months)
- Patterns of failure(12 months)
- Steroid needs until treatment failure(12 months)
- Objective response rates(12 months)
研究者
Maciej Harat
dr hab. n. med. Maciej Harat prof. UMK
Prof. Franciszek Lukaszczyk Memorial Oncology Center