Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma: A Phase Ib Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 10
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a three parallel cohort, open-labeled, non-randomized, multicenter study. All three cohorts will enroll independently.
详细描述
Group A will be composed of newly-diagnosed, elderly patients with Isocitrate dehydrogenase 1 (IDH1) gene non mutant (IDH1R132H) and O-6-methylguanine-DNA methyltransferase (MGMT) promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and radiotherapy (RT).
Group B will be composed of newly-diagnosed, elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.
For both Groups A and B, there will be a classical 3+3 dose escalation and an expansion phase in the study. Up to a total of 24 evaluable patients in Group A and up to a total of 12 evaluable patients in Group B (up to 36 evaluable patients for Groups A and B).
Group C patients will be composed of patients initially diagnosed with IDH1R132H-non-mutant anaplastic astrocytoma or glioblastoma at first relapse post TMZ/RT-->TMZ therapy who will receive TG02.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group C - TG02
Patients initially diagnosed with anaplastic astrocytoma or glioblastoma at first relapse post TMZ/RT --> TMZ therapy who will receive TG02.
干预措施: TG02 (Drug)
Group A - TG02 + RT
Elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and radiation therapy.
干预措施: TG02 (Drug)
Group A - TG02 + RT
Elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and radiation therapy.
干预措施: Radiation Therapy (Radiation)
Group B - TG02 + TMZ
Elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.
干预措施: TG02 (Drug)
Group B - TG02 + TMZ
Elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: From the initiation of TG02 treatment until the determination of the Maximum Tolerated Dose (MTD) for each participant, which is expected to occur within the first 28-day cycle for most participants.
The primary objective in Groups A and B of the EORTC-1608 study is to establish the Maximum Tolerated Dose (MTD) of TG02 and the recommended phase II dose when combined with either radiotherapy (Group A) or temozolomide (Group B) for glioblastoma treatment. The MTD is the highest dose where no more than one of six patients experiences a Dose Limiting Toxicity (DLT). The study requires a 75% dose intensity for TG02 and the concurrent treatment. The trial uses a two-cohort design to assess TG02 with hypofractionated radiotherapy in patients with an unmethylated MGMT promoter or with temozolomide in those with a methylated promoter. Dose escalation begins at 100 mg TG02 twice weekly. If no DLTs occur in the first three patients, the dose increases to 150 mg. If one patient has a DLT, three more are enrolled at the same dose. If no further DLTs occur, escalation continues. If more than one patient has a DLT, escalation stops, and the previous dose is the MTD.
Percentage of Participants Maintaining Progression-free Survival at 6 Months (PFS-6)
时间窗: The time frame for assessing PFS spans from the date of consent to either disease progression or death. Data are specifically presented for the 6-month time point.
The primary endpoint for Group C is Progression-free survival at 6 months (PFS-6), assessed by Response Assessment in Neuro-Oncology (RANO) criteria. Complete Response (CR) is defined as the disappearance of all enhancing measurable and nonmeasurable disease for at least 4 weeks. Partial Response (PR) requires at least a 50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions for at least 4 weeks. Stable Disease (SD) is when the patient does not qualify for CR, PR, or progression, with stable nonenhancing lesions on the same or lower dose of corticosteroids. Progression (PD) is defined as at least a 25% increase in the sum of products of perpendicular diameters of enhancing lesions compared to the smallest measurement at baseline or best response, a significant increase in T2/FLAIR lesion, any new lesion, or clear clinical deterioration not attributable to other causes.
次要结局
- Progression-free Survival(The time frame for assessing PFS is the duration from the date of consent until disease progression or death. PFS was assessed by its median the point time at which 50% of the patients have experienced death.)
- Overall Survival (OS)(The time frame for assessing OS is from consent to the date until death or the end of the study, whichever comes first. OS was assessed by its median the point time at which 50% of the patients have experienced death.)
- Objective Response(Time frame for assessing response is from the initiation of treatment with TG02 until disease progression or death. It was not assessed at specific time point but throughout the study. The OR rate is determined based on the best response observed.)
- Neurological Progression-free Survival(The time frame for assessing NPFS spans from the date of consent to either disease progression or death.NPFS was assessed by its median the point time at which 50% of the patients have experienced death.)