A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
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.
Study details:
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 10 patients will take part in this study. It is anticipated this research study will enable investigators to objectively measure the biological activity of Safusidenib in patients with IDH1 mutated LGG.
Anti-tumour activity will be assessed by RANO response criteria. The investigators have previous experience in pre-treating patients with GBM prior to surgery with systemic therapies and collecting tumour, peri-tumour and normal brain tissues for PK, PD and biomarker evaluation.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- EARLY_PHASE1
Study ID
NCT05577416
Intervention or treatment
PROCEDURE: Biopsy
DRUG: Part A: Safusidenib Erbumine
PROCEDURE: Surgery (maximal resection)
DRUG: Part B: Safusidenib Erbumine
Conditions
- Glioma
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Research sites nearby
Closest Location:
Royal Melbourne Hospital
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Royal Melbourne Hospital
Melbourne, Victoria, Australia
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Who is running the clinical trial?
Melbourne Health
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Safusidenib Erbumine (AB-218)
| Procedure: Biopsy, Drug: Part A: Safusidenib Erbumine, Procedure: Surgery (maximal resection), Drug: Part B: Safusidenib Erbumine |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Phase 0: Feasibility of Phase 0 study in patient population | Number of patients to complete all planned investigations and procedures | 14 months |
| Phase 0: pharmacokinetic analysis of tumour tissue | Total and unbound AB-218 in tumour tissue | 4 weeks |
| Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF) | Total and unbound AB-218 in CSF | 4 weeks |
| Phase 2: Number of Adverse events | Number of adverse events (AEs) according to NCI CTCAE v 5 | up to 30 days after last study dose |
| Phase 2: Incidence of drug related adverse events | Drug related adverse events | up to 30 days after last study dose |
| Phase 2: Incidence of dose limiting toxicity | Dose limiting toxicity events | up to 30 days after last study dose |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Phase 0: Incidence of treatment emergent Adverse events | Treatment emergent adverse events (AEs) according to NCI CTCAE v 5 | 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-day morbidity and mortality post surgery | 30 days after maximal resection |
| Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour | Changes in 2-hydroxyglutarate (2-HG) levels in tumour | after maximal resection (4 weeks), at progression (optional) |
| Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF) | Changes in 2-hydroxyglutarate (2-HG) levels in cerebrospinal fluid (CSF) | after maximal resection (4 weeks), at progression (optional) |
| Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma | Changes in 2-hydroxyglutarate (2-HG) levels in plasma | after maximal resection (4 weeks), monthly during treatment, at progression (optional) |
| Phase 0: anti-tumour activity | Objective response (LGG RANO assessment) | 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) | Understanding the patients' perspective on the peri-operative design and satisfaction with study procedures | 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) | Understanding the patients' perspective on the peri-operative design and satisfaction with study procedures | 4 months post op |
| Phase 2: anti-tumour activity | Objective response (LGG RANO assessment) | 12 weekly until progression |
References
Clinical Trials Gov: A Study of AB-218 in Patients With IDH1 Mutated Low Grade GliomaOther trials to consider
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