A Phase 3, Multicenter, Randomized, Double-blind, Placebo- Controlled Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Servier
- 入组人数
- 57
- 试验地点
- 9
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The objective of this study is to determine the efficacy, safety, and pharmacokinetics of vorasidenib in Asian participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation. The study will begin with a safety lead-in (SLI) phase and then will transition to a randomized double-blind placebo-controlled phase. During the study participants will have study visits on day 1 and 15 of the first two cycles, and then only on day 1 of treatment cycles in the frequency included in the study schedule of assessments. All participants will have an end of treatment visit within 7 days after their last dose of study treatment. Approximately 28 (+5) days after treatment has ended, a safety follow-up visit will occur. Study visits may include questionnaires, blood tests, ECG, vital signs, and a physical examination. Beginning at the end of treatment visit participants will be contacted by phone every 6 months for overall survival up to 5 years after the last participant is randomized or until death, withdrawal of consent from overall study participation, lost to follow-up, or sponsor ending the study, whichever occurs first.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be at least 12 years of age (for Randomized Double-Blind phase) and weigh at least 40 kg.
- •Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or Lansky Play Performance Scale (LPPS) score (for participants <16 years of age) of ≥80%.
- •Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
- •Have had at least 1 prior surgery for glioma with the most recent one having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before randomization, and no other prior anticancer therapy, including radiotherapy and not be in need of immediate chemotherapy or radiotherapy.
- •Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease
- •Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC for double blind part.
排除标准
- •Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc.
- •Concurrent active malignancy except for a) curatively resected nonmelanoma skin cancer or b) curatively treated carcinoma in situ. Participants with previously treated malignancies are eligible provided they have been disease-free for 3 years at Screening.
- •Have any other acute or chronic medical or psychiatric condition that may increase the risk associated with the study participation or investigational product administration or may interfere with the interpretation of study results.
- •Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, known positive human immunodeficiency virus antibody results, or AIDS-related illness. Participants with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Participants with chronic HBV that is adequately suppressed by institutional practice will be permitted.
研究组 & 干预措施
Randomized Double-Blind Phase: Placebo
干预措施: Placebo (Drug)
Randomized Double-Blind Phase: Vorasidenib
干预措施: Vorasidenib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Approximately 1.5 years
The time from date of randomization to date of first documented radiographic progressive disease (PD), as assessed by the Blinded Independent Review Committee (BIRC), or date of death due to any cause, whichever occurs earlier.
次要结局
- Dose limiting toxicities (DLTs) (for open-label Safety Lead In (SLI) phase)(Through Cycle 1 (28 days))
- Number of adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death(Through the safety follow up visit, 28 days after the last dose (approximately 6.5 years))
- Severity of AEs(Through the safety follow up visit, 28 days after the last dose (approximately 6.5 years))
- Time-To-Next-Intervention (TTNI)(Through the PFS Follow-up (approximately 6.5 years))
- Tumor Growth Rate (TGR) as assessed by volume(Through the PFS Follow-up (approximately 6.5 years))
- Objective response(Through the PFS Follow-up (approximately 6.5 years))
- Time to response(Through the PFS Follow-up (approximately 6.5 years))
- Duration of response(Through the PFS Follow-up (approximately 6.5 years))
- Overall survival(Through the Overall Survival Follow-up (approximately 6.5 years))
- Plasma concentrations of vorasidenib(Through the end of treatment visit, within 7 days after the last dose (approximately 6.5 years))
- Number of seizures by month(Through the end of treatment visit, within 7 days after the last dose (approximately 6.5 years))