A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
- Conditions
- Glioma
- Interventions
- Procedure: BiopsyProcedure: Surgery (maximal resection)
- Registration Number
- NCT05577416
- Lead Sponsor
- Melbourne Health
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
- 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
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
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Tumour involves cerebellum or brainstem
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Patients who have undergone surgery for glioma within 24 months of study enrolment
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Patients who have received prior chemotherapy and / or radiation for a diagnosis of glioma
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Patients with contraindications to MRI or unwilling to undergo MRI
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History of central nervous system bleeding as defined by stroke within 6 months before enrolment
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Evidence of acute intracranial / intra-tumoural haemorrhage, except for participants with stable grade 1 haemorrhage
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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
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Safusidenib Erbumine (AB-218) Biopsy Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2) Safusidenib Erbumine (AB-218) Surgery (maximal resection) Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
- Primary Outcome Measures
Name Time Method Phase 0: Feasibility of Phase 0 study in patient population 14 months Number of patients to complete all planned investigations and procedures
Phase 2: Incidence of dose limiting toxicity up to 30 days after last study dose Dose limiting toxicity events
Phase 0: pharmacokinetic analysis of tumour tissue 4 weeks Total and unbound AB-218 in tumour tissue
Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF) 4 weeks Total and unbound AB-218 in CSF
Phase 2: Number of Adverse events 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 up to 30 days after last study dose Drug related adverse events
- Secondary Outcome Measures
Name Time Method Phase 0: Incidence of treatment emergent Adverse events during 1 cycle of AB-128, prior to maximal resection (4 weeks) Treatment emergent adverse events (AEs) according to NCI CTCAE v 5
Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218 30 days after maximal resection 30-day morbidity and mortality post surgery
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour after maximal resection (4 weeks), at progression (optional) Changes in 2-hydroxyglutarate (2-HG) levels in tumour
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF) after maximal resection (4 weeks), at progression (optional) Changes in 2-hydroxyglutarate (2-HG) levels in cerebrospinal fluid (CSF)
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma after maximal resection (4 weeks), monthly during treatment, at progression (optional) Changes in 2-hydroxyglutarate (2-HG) levels in plasma
Phase 0: anti-tumour activity 4 weeks Objective response (LGG RANO assessment)
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 Understanding the patients' perspective on the peri-operative design and satisfaction with study procedures
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 Understanding the patients' perspective on the peri-operative design and satisfaction with study procedures
Phase 2: anti-tumour activity 12 weekly until progression Objective response (LGG RANO assessment)
Trial Locations
- Locations (1)
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia