A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma

Trial Title: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma

NCT ID: NCT05577416

Condition: Glioma

Conditions: Official terms:
Glioma

Conditions: Keywords:
IDH1
Diffuse Astrocytoma
oligodendroglioma
phase 0
perioperative

Study type: Interventional

Study phase: Early Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: Phase 0 'window of opportunity'/perioperative (Part A) followed by Phase 2 adjuvant treatment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: Biopsy
Description: Patients will undergo stereotactic biopsy by craniotomy or burr hole.
Arm group label: Safusidenib Erbumine (AB-218)

Intervention type: Drug
Intervention name: Part A: Safusidenib Erbumine
Description: Part A: Safusidenib Erbumine orally 250 mg BID for 28 days.
Arm group label: Safusidenib Erbumine (AB-218)

Intervention type: Procedure
Intervention name: Surgery (maximal resection)
Description: Surgery: Maximal safe resection, within 24 hours of last dose of Safusidenib Erbumine.
Arm group label: Safusidenib Erbumine (AB-218)

Intervention type: Drug
Intervention name: Part B: Safusidenib Erbumine
Description: Part B: Safusidenib Erbumine orally 250 mg BID for 28 days for a minimum of 12, 28-day cycles subject to ongoing documented evidence of clinical benefit, until disease progression or unacceptable toxicity.
Arm group label: Safusidenib Erbumine (AB-218)

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

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Royal Melbourne Hospital

Address:
City: Melbourne
Country: Australia

Status: Recruiting

Contact:
Last name: Kate Drummond

Start date: October 11, 2022

Completion date: December 1, 2025

Lead sponsor:
Agency: Melbourne Health
Agency class: Other

Collaborator:
Agency: Walter and Eliza Hall Institute of Medical Research
Agency class: Other

Collaborator:
Agency: AnHeart Therapeutics Inc.
Agency class: Industry

Source: Melbourne Health

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05577416