Back to resultsA Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma (AB-218-IIT-201)
Primary Purpose
Glioma
Status
Recruiting
Phase
Early Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Biopsy
Part A: AB-218
Surgery (maximal resection)
Part B: AB-218
Sponsored by
About this trial
This is an interventional treatment trial for Glioma focused on measuring IDH1, Diffuse Astrocytoma, oligodendroglioma, phase 0, perioperative
Eligibility Criteria
Inclusion Criteria:
- Patients will have a radiological diagnosis of LGG or a previously confirmed LGG and be planned for elective, non-urgent resection of the tumour
- Patients who do not require urgent resection for mass effect, cerebral oedema or hydrocephalus in the opinion of the treating neurosurgeon
- Tumour size 2 - 5 cm
- Measurable and/or evaluable disease as per LGG-RANO criteria
- Willing to undergo planned surgical procedures
Routine trial inclusion criteria
- Adults ≥ 18 < 40 years of age
- ECOG performance score 0 - 1
- Life expectancy of at least 24 months
- Haematological and renal function as prescribed
- Hepatic function with prescribed limits
- Reproductive and contraception criteria as prescribed
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from participation in the study:
- Patients who require urgent resection due to degree of mass effect, oedema, hydrocephalus or symptoms
- Patients who have received chemotherapy or radiation for the diagnosis of LGG
- Tumour involves cerebellum or brainstem
Routine trial exclusion criteria
- Any significant Intracranial bleeding in the opinion of the principal investigator
- Prior malignancy
- Significant co-morbidity
- ECG abnormalities
- Recent surgery
- Known allergy or sensitivity to any of the excipients in the investigational product
Sites / Locations
- Royal Melbourne HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AB-218
Arm Description
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
Outcomes
Primary Outcome Measures
Phase 0: Feasibility of Phase 0 study in patient population
Number of patients to complete all planned investigations and procedures
Phase 0: pharmacokinetic analysis of tumour tissue
Total and unbound AB-218 in tumour tissue
Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)
Total and unbound AB-218 in CSF
Phase 2: Number of Adverse events
Number of adverse events (AEs) according to NCI CTCAE v 5
Phase 2: Incidence of drug related adverse events
Drug related adverse events
Phase 2: Incidence of dose limiting toxicity
Dose limiting toxicity events
Secondary Outcome Measures
Phase 0: Incidence of treatment emergent Adverse events
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-day morbidity and mortality post surgery
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour
Changes in 2-hydroxyglutarate (2-HG) levels in tumour
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF)
Changes in 2-hydroxyglutarate (2-HG) levels in cerebrospinal fluid (CSF)
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma
Changes in 2-hydroxyglutarate (2-HG) levels in plasma
Phase 0: anti-tumour activity
Objective response (LGG RANO assessment)
Phase 2: anti-tumour activity
Objective response (LGG RANO assessment)
Full Information
NCT ID
NCT05577416
First Posted
September 19, 2022
Last Updated
October 11, 2022
Sponsor
Melbourne Health
Collaborators
Walter and Eliza Hall Institute of Medical Research, AnHeart Therapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05577416
Brief Title
A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
Acronym
AB-218-IIT-201
Official Title
A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2022 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Melbourne Health
Collaborators
Walter and Eliza Hall Institute of Medical Research, AnHeart Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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 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 up to 12 cycles of AB-218.
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 AB-218 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma
Keywords
IDH1, Diffuse Astrocytoma, oligodendroglioma, phase 0, perioperative
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase 0 'window of opportunity'/perioperative (Part A) followed by Phase 2 adjuvant treatment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AB-218
Arm Type
Experimental
Arm Description
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Intervention Description
Patients will undergo stereotactic biopsy by craniotomy or burr hole.
Intervention Type
Drug
Intervention Name(s)
Part A: AB-218
Intervention Description
Part A: AB-218 orally 250 mg BID for 28 days.
Intervention Type
Procedure
Intervention Name(s)
Surgery (maximal resection)
Intervention Description
Surgery: Maximal safe resection, within 24 hours of last dose of AB-218.
Intervention Type
Drug
Intervention Name(s)
Part B: AB-218
Intervention Description
Part B: AB-218 orally 250 mg BID for 28 days for up to 12 cycles.
Primary Outcome Measure Information:
Title
Phase 0: Feasibility of Phase 0 study in patient population
Description
Number of patients to complete all planned investigations and procedures
Time Frame
14 months
Title
Phase 0: pharmacokinetic analysis of tumour tissue
Description
Total and unbound AB-218 in tumour tissue
Time Frame
4 weeks
Title
Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)
Description
Total and unbound AB-218 in CSF
Time Frame
4 weeks
Title
Phase 2: Number of Adverse events
Description
Number of adverse events (AEs) according to NCI CTCAE v 5
Time Frame
up to 30 days after last study dose
Title
Phase 2: Incidence of drug related adverse events
Description
Drug related adverse events
Time Frame
up to 30 days after last study dose
Title
Phase 2: Incidence of dose limiting toxicity
Description
Dose limiting toxicity events
Time Frame
up to 30 days after last study dose
Secondary Outcome Measure Information:
Title
Phase 0: Incidence of treatment emergent Adverse events
Description
Treatment emergent adverse events (AEs) according to NCI CTCAE v 5
Time Frame
during 1 cycle of AB-128, prior to maximal resection (4 weeks)
Title
Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218
Description
30-day morbidity and mortality post surgery
Time Frame
30 days after maximal resection
Title
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour
Description
Changes in 2-hydroxyglutarate (2-HG) levels in tumour
Time Frame
after maximal resection (4 weeks), at progression (optional)
Title
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF)
Description
Changes in 2-hydroxyglutarate (2-HG) levels in cerebrospinal fluid (CSF)
Time Frame
after maximal resection (4 weeks), at progression (optional)
Title
Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma
Description
Changes in 2-hydroxyglutarate (2-HG) levels in plasma
Time Frame
after maximal resection (4 weeks), monthly during treatment, at progression (optional)
Title
Phase 0: anti-tumour activity
Description
Objective response (LGG RANO assessment)
Time Frame
4 weeks
Title
Phase 2: anti-tumour activity
Description
Objective response (LGG RANO assessment)
Time Frame
8 weekly until progression
Other Pre-specified Outcome Measures:
Title
Phase 2: Survival
Description
Progression free survival (PFS)
Time Frame
30 days after last study dose
Title
Phase 2: Survival
Description
Overall survival (OS)
Time Frame
30 days after last study dose
Title
Phase 2: Survival
Description
Time to treatment failure (TTF)
Time Frame
30 days after last study dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients will have a radiological diagnosis of LGG or a previously confirmed LGG and be planned for elective, non-urgent resection of the tumour
Patients who do not require urgent resection for mass effect, cerebral oedema or hydrocephalus in the opinion of the treating neurosurgeon
Tumour size 2 - 5 cm
Measurable and/or evaluable disease as per LGG-RANO criteria
Willing to undergo planned surgical procedures
Routine trial inclusion criteria
Adults ≥ 18 < 40 years of age
ECOG performance score 0 - 1
Life expectancy of at least 24 months
Haematological and renal function as prescribed
Hepatic function with prescribed limits
Reproductive and contraception criteria as prescribed
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from participation in the study:
Patients who require urgent resection due to degree of mass effect, oedema, hydrocephalus or symptoms
Patients who have received chemotherapy or radiation for the diagnosis of LGG
Tumour involves cerebellum or brainstem
Routine trial exclusion criteria
Any significant Intracranial bleeding in the opinion of the principal investigator
Prior malignancy
Significant co-morbidity
ECG abnormalities
Recent surgery
Known allergy or sensitivity to any of the excipients in the investigational product
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kate Drummond, Prof
Phone
+61 3 9345 2767
Email
AnHeart@wehi.edu.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kate Drummond, Prof
Organizational Affiliation
Melbourne Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kate Drummond
12. IPD Sharing Statement
Learn more about this trial
A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
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