Clinical trial NCT05577416: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
Official title: A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Glioma
Keywords: IDH1
Diffuse Astrocytoma
oligodendroglioma
phase 0
perioperative
Lead sponsor: Melbourne Health
Sponsor class: OTHER
Collaborators: name: Walter and Eliza Hall Institute of Medical Research
name: AnHeart Therapeutics Inc.
First posted: 2022-10-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 0 'window of opportunity'/perioperative (Part A) followed by Phase 2 adjuvant treatment
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed LGG or new diagnosis of LGG based on MRI
2. Tumours suitable for biopsy and safe for maximal resection in the opinion of the treating neurosurgeon
3. Patients who in the consensus of the treating neurosurgeon require resection of the brain tumour.
4. Patients who do not require immediate definitive resection of the brain tumour in the opinion of the treating neurosurgeon
5. Measurable and/or evaluable disease as per LGG-RANO criteria
6. Age ≥ 18 years of age.
7. ECOG performance score 0-1
8. Life expectancy of at least 24 months, in the opinion of the investigator
9. Adequate haematological, renal and hepatic function
10. Reproductive and contraception criteria as prescribed

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from participation in the study:

1. Patients who require immediate definitive resection due to degree of mass effect or symptoms
2. Multicentric / multifocal tumour
3. Tumour involves cerebellum or brainstem
4. Patients who have undergone surgery for glioma within 24 months of study enrolment
5. Patients who have received prior chemotherapy and / or radiation for a diagnosis of glioma
6. Patients with contraindications to MRI or unwilling to undergo MRI
7. History of central nervous system bleeding as defined by stroke within 6 months before enrolment
8. Evidence of acute intracranial / intra-tumoural haemorrhage, except for participants with stable grade 1 haemorrhage
9. 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
10. 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

Primary outcomes:
measure: Phase 0: Feasibility of Phase 0 study in patient population
timeFrame: 14 months
measure: Phase 0: pharmacokinetic analysis of tumour tissue
timeFrame: 4 weeks
measure: Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)
timeFrame: 4 weeks
measure: Phase 2: Number of Adverse events
timeFrame: up to 30 days after last study dose
measure: Phase 2: Incidence of drug related adverse events
timeFrame: up to 30 days after last study dose
measure: Phase 2: Incidence of dose limiting toxicity
timeFrame: up to 30 days after last study dose
Secondary outcomes:
measure: Phase 0: Incidence of treatment emergent Adverse events
timeFrame: during 1 cycle of AB-128, prior to maximal resection (4 weeks)
measure: Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218
timeFrame: 30 days after maximal resection
measure: Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour
timeFrame: after maximal resection (4 weeks), at progression (optional)
measure: Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF)
timeFrame: after maximal resection (4 weeks), at progression (optional)
measure: Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma
timeFrame: after maximal resection (4 weeks), monthly during treatment, at progression (optional)
measure: Phase 0: anti-tumour activity
timeFrame: 4 weeks
measure: 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)
timeFrame: 4 months post op
measure: 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)
timeFrame: 4 months post op
measure: Phase 2: anti-tumour activity
timeFrame: 12 weekly until progression
Other outcomes:
measure: Phase 2: Survival
timeFrame: 30 days after last study dose
measure: Phase 2: Survival
timeFrame: 30 days after last study dose
measure: Phase 2: Survival
timeFrame: 30 days after last study dose
measure: Phase 0: Change in tumour volume in response to Safusidenib
timeFrame: 4 weeks
measure: Phase 2: Change in tumour volume in response to Safusidenib
timeFrame: 12 weekly until progression
Locations:
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Melbourne Health
name: Kate Drummond, Prof
role: PRINCIPAL_INVESTIGATOR
References: