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

Glioma Clinical Trial

— AB-218-IIT-201  

Official title:

A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05577416
• Other study ID #: 2022.003
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 11, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: March 2024
• Source: Melbourne Health
• Contact: Kate Drummond, Prof
• Phone: +61 3 9345 2767
• Email: AnHeart[@]wehi.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioma

Intervention

Procedure:
• Biopsy
Patients will undergo stereotactic biopsy by craniotomy or burr hole.

Drug:
• Part A: Safusidenib Erbumine
Part A: Safusidenib Erbumine orally 250 mg BID for 28 days.

Procedure:
• Surgery (maximal resection)
Surgery: Maximal safe resection, within 24 hours of last dose of Safusidenib Erbumine.

Drug:
• Part B: Safusidenib Erbumine
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.

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Melbourne	Victoria

Sponsors (3)

Lead Sponsor	Collaborator
Melbourne Health	AnHeart Therapeutics Inc., Walter and Eliza Hall Institute of Medical Research

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Phase 2: Survival	Progression free survival (PFS)	30 days after last study dose
Other	Phase 2: Survival	Overall survival (OS)	30 days after last study dose
Other	Phase 2: Survival	Time to treatment failure (TTF)	30 days after last study dose
Other	Phase 0: Change in tumour volume in response to Safusidenib	Volumetric analysis of post biopsy and pre-op MRI images	4 weeks
Other	Phase 2: Change in tumour volume in response to Safusidenib	Volumetric analysis of MRI images during adjuvant treatment	12 weekly until progression
Primary	Phase 0: Feasibility of Phase 0 study in patient population	Number of patients to complete all planned investigations and procedures	14 months
Primary	Phase 0: pharmacokinetic analysis of tumour tissue	Total and unbound AB-218 in tumour tissue	4 weeks
Primary	Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)	Total and unbound AB-218 in CSF	4 weeks
Primary	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
Primary	Phase 2: Incidence of drug related adverse events	Drug related adverse events	up to 30 days after last study dose
Primary	Phase 2: Incidence of dose limiting toxicity	Dose limiting toxicity events	up to 30 days after last study dose
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Phase 0: anti-tumour activity	Objective response (LGG RANO assessment)	4 weeks
Secondary	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
Secondary	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
Secondary	Phase 2: anti-tumour activity	Objective response (LGG RANO assessment)	12 weekly until progression