A Prospective, Randomized, Single-center Trial of NovoTTF-200A Together With Radiation Therapy and Temozolomide Compared to Radiation Therapy and Temozolomide Alone in Patients With Newly Diagnosed GBM
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- PFS12
研究概览
简要总结
Study Objectives: To compare the efficacy and safety outcome of newly diagnosed GBM patients treated with NovoTTF-200A concomitant to RT and TMZ to those treated with RT and TMZ alone Study Design: Prospective, randomized, open label, standard of care control Study Hypothesis: The hypothesis of this study is that addition of NovoTTF-200A treatment to RT and TMZ will significantly increase progression free survival of newly diagnosed GBM patients compared to patients treated with RT and TMZ alone Sample Size: 60 patients with newly diagnosed GBM Study Population: Patients with tissue based diagnosis of GBM, above 18 years of age, of both genders after surgery or biopsy amenable for radiation therapy (RT) with concomitant TMZ (Stupp protocol1)
Primary endpoint:
Rate of progression-free survival at 12 months (PFS12)
Secondary endpoints:
- Overall survival (OS)
- Progression-free survival (PFS)
- Progression free survival at 6 months (PFS6)
- 1 and 2-year survival rates
- Overall radiological response (ORR, per RANO criteria)
- Safety (adverse events severity and frequency)
详细描述
Glioblastoma (GBM), a malignant form of astrocytoma, is the most common primary intracranial neoplasm in adults2. The incidence of GBM increases steadily above 45 years of age with a prevalence of approximately 7500 cases in the USA. Despite numerous attempts to improve the outcome of patients with GBM, the 3-year survival of patients treated with maximal surgical resection when feasible, 60 Gy radiotherapy (RT) together with concomitant temozolomide (TMZ) (RT/TMZ), followed by maintenance (adjuvant) TMZ for 6 months was only 6% with median survival of 14.6 months1. In a prospective phase 3 trial, the addition of TTFields (200 kHz) to maintenance temozolomide increased the median overall survival of patients enrolled in the study following RT/TMZ to 20.9 months, compared with 16.0 months only in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001).
TTFields are a novel treatment modality for the treatment of malignant tumors that is also referred to as the fourth modality of cancer treatment in addition to surgery, radiation therapy, and chemotherapy. Pre-clinical studies3-9 have shown this treatment modality to effectively inhibit the growth of experimental tumors both in-vitro and in-vivo without any systemic side effects. Large-scale, phase III clinical studies have validated the safety and efficacy of TTFields in patients with recurrent and newly diagnosed glioblastoma10,11. TTFields has now been approved as a standard treatment for GBM by most of the regulatory agencies around the world and its application is steadily increasing worldwide.
Standard Treatment of GBM
The currently accepted standard treatment of newly diagnosed GBM is based on: surgical resection to the extent safely feasible followed by RT with concomitant TMZ, followed by adjuvant TMZ chemotherapy in combination with TTFields. Each of these treatments is briefly described below:
- Surgical resection - Treatment of patients with GBM usually consists of tumor resection (to the extent safely feasible) or diagnostic biopsy.
- Radiotherapy (RT) - Post-surgical RT improves survival, though even with maximal treatment, survival after RT alone is still limited to about one year1.
- Temozolomide (TMZ) - Concomitant TMZ chemotherapy during RT and adjuvant (maintenance) TMZ for 6 cycles has been shown to significantly improve survival (HR 0.63). This combined modality treatment is considered the standard of care.
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
- 是
入选标准
- •Histologically confirmed diagnosis of GBM according to WHO classification criteria.
- •age ≥ 18 years
- •Recovered from debulking surgery or biopsy-only.
- •Planned treatment with RT/TMZ following 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 effective contraception.
- •All patients must sign written informed consent.
- •Stable or decreasing dose of corticosteroids for the last 7 days prior to randomization, if applicable.
排除标准
- •Early progressive disease before initiation of TMZ/RT.
- •Participation in another clinical treatment trial
- •Pregnancy
- •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)
- •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.
结局指标
主要结局
PFS12
时间窗: 12 months
Rate of progression-free survival at 12 months
次要结局
- PFS6(6 months)
- One and two year survival rate(24 months)
- Radiological response(26 months)
- adverse events(36 months)