A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Phase 0: Feasibility of Phase 0 study in patient population
研究概览
简要总结
The aim of this clinical trial is to evaluate the feasibility of undertaking a Phase 0 surgical study in patients with diagnosis of a IDH1 mutated Low Grade Glioma (LGG) who have not received prior radiation or chemotherapy and are planned to undergo surgical resection.
详细描述
This is a single arm, open label Phase 0 trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with AB-218 following biopsy and prior to resection in patients with IDH1 mutated glioma.
Participants will receive treatment in 2 parts:
Part A: Biopsy followed by 1 cycle (28 days) of Safusidenib Erbumine (formerly AB-218), an orally available, small molecular inhibitor of mutated IDH1, then safe maximal resection of the tumour.
Part B: Following recovery from surgery, patients will receive at least 12 cycles of Safusidenib, subject to ongoing documented evidence of clinical benefit, until disease progression or unacceptable toxicity.
It is expected that 15 patients will take part in this study.
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
- •Histologically confirmed LGG or new diagnosis of LGG based on MRI
- •Tumours suitable for biopsy and safe for maximal resection in the opinion of the treating neurosurgeon
- •Patients who in the consensus of the treating neurosurgeon require resection of the brain tumour.
- •Patients who do not require immediate definitive resection of the brain tumour in the opinion of the treating neurosurgeon
- •Measurable and/or evaluable disease as per LGG-RANO criteria
- •Age ≥ 18 years of age.
- •ECOG performance score 0-1
- •Life expectancy of at least 24 months, in the opinion of the investigator
- •Adequate haematological, renal and hepatic function
- •Reproductive and contraception criteria as prescribed
排除标准
- •Patients who meet any of the following criteria will be excluded from participation in the study:
- •Patients who require immediate definitive resection due to degree of mass effect or symptoms
- •Multicentric / multifocal tumour
- •Tumour involves cerebellum or brainstem
- •Patients who have undergone surgery for glioma within 24 months of study enrolment
- •Patients who have received prior chemotherapy and / or radiation for a diagnosis of glioma
- •Patients with contraindications to MRI or unwilling to undergo MRI
- •History of central nervous system bleeding as defined by stroke within 6 months before enrolment
- •Evidence of acute intracranial / intra-tumoural haemorrhage, except for participants with stable grade 1 haemorrhage
- •Other general criteria including:
- •i) ECG abnormalities ii) significant comorbidity or infection iii) Prior malignancy iv) Recent surgery v) Known allergy or sensitivity to any of the excipients in the investigational product vi) no contraindicated concomitant medications
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
研究组 & 干预措施
Safusidenib Erbumine (AB-218)
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
干预措施: Biopsy (Procedure)
Safusidenib Erbumine (AB-218)
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
干预措施: Surgery (maximal resection) (Procedure)
Safusidenib Erbumine (AB-218)
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
干预措施: Part A: Safusidenib Erbumine (Drug)
Safusidenib Erbumine (AB-218)
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
干预措施: Part B: Safusidenib Erbumine (Drug)
结局指标
主要结局
Phase 0: Feasibility of Phase 0 study in patient population
时间窗: 14 months
Number of patients to complete all planned investigations and procedures
Phase 2: Incidence of dose limiting toxicity
时间窗: up to 30 days after last study dose
Dose limiting toxicity events
Phase 0: pharmacokinetic analysis of tumour tissue
时间窗: 4 weeks
Total and unbound AB-218 in tumour tissue
Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)
时间窗: 4 weeks
Total and unbound AB-218 in CSF
Phase 2: Number of Adverse events
时间窗: up to 30 days after last study dose
Number of adverse events (AEs) according to NCI CTCAE v 5
Phase 2: Incidence of drug related adverse events
时间窗: up to 30 days after last study dose
Drug related adverse events
次要结局
- Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour(after maximal resection (4 weeks), at progression (optional))
- Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF)(after maximal resection (4 weeks), at progression (optional))
- Phase 0: Incidence of treatment emergent Adverse events(during 1 cycle of AB-128, prior to maximal resection (4 weeks))
- Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218(30 days after maximal resection)
- Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma(after maximal resection (4 weeks), monthly during treatment, at progression (optional))
- Phase 0: anti-tumour activity(4 weeks)
- Phase 0: Identify factors that can improve the patient experience quality of the service provided to participants using Research Participant Perception Survey short form (RPPS)(4 months post op)
- Phase 2: Identify factors that can improve the patient experience quality of the service provided to participants using Research Participant Perception Survey short form (RPPS)(4 months post op)
- Phase 2: anti-tumour activity(12 weekly until progression)