A Phase 1, Multicenter, Randomized, Controlled, Open-Label, Perioperative Study of AG-120 and AG-881 in Subjects With Recurrent, Non-Enhancing, IDH1 Mutant, Low Grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 6
- 主要终点
- 2-HG concentration in surgically resected tumors
研究概览
简要总结
Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.
详细描述
A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for patients who require surgery. The purpose of this study is to evaluate the suppression of 2-HG by comparing the concentration of 2-HG in resected tumors from IDH1 mutant glioma subjects following AG-120 or AG-881 treatment with the 2-HG concentration in untreated, control tumors. The safety, tolerability, PK/PD, and anti tumor activity data from the study in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for future studies in glioma.
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
- •Be ≥18 years of age.
- •Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification).
- •Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
- •Have central confirmation of primarily non-enhancing disease by MRI with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring 1×1×1 cm.
- •Be candidates for clinical resection but for whom surgery is not urgently indicated (eg, for whom surgery within the next 2-4 months is appropriate).
- •Have KPS of ≥60%
- •Have expected survival of ≥12 months.
排除标准
- •Have received prior systemic anti-cancer therapy within 1 month of the first dose of AG-120 or AG-881 or have received an investigational agent <14 days prior to their first dose of AG-120 or AG-
- •In addition, the first dose of AG-120 or AG-881 should not occur before a period of ≥5 half-lives of the investigational agent has elapsed.
- •Have had radiation within 6 months of the first dose of AG-120 or AG-
- •(Note: Prior biopsy or surgery is allowed.)
- •Have received any prior treatment with an IDH inhibitor.
- •Have received any prior treatment with bevacizumab (Avastin).
研究组 & 干预措施
AG-120
AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 .
干预措施: AG-120 (Drug)
AG-881
AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-881.
干预措施: AG881 (Drug)
No Treatment Pre-Surgery
Subjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881.
结局指标
主要结局
2-HG concentration in surgically resected tumors
时间窗: Up to 4 weeks, on average
次要结局
- Safety and tolerability: incidence of adverse events and serious adverse events(Up to 48 weeks, on average)
- Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.(Up to 4 weeks, on average)
- Peak Plasma Concentration (Cmax) of AG-120 or AG-881(Up to 4 weeks, on average)
- Time to maximum concentration (Tmax) of AG-120 or AG-881(Up to 4 weeks, on average)
- Area Under the Curve (AUC) of AG-120 or AG-881(Up to 4 weeks, on average)
- Elimination half-life of AG-120 or AG-881(Up to 4 weeks, on average)
- Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.(Up to 48 weeks, on average)