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A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma (AB-218-IIT-201)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05577416
Recruitment Status : Recruiting
First Posted : October 13, 2022
Last Update Posted : October 13, 2022
Sponsor:
Collaborators:
Walter and Eliza Hall Institute of Medical Research
AnHeart Therapeutics Inc.
Information provided by (Responsible Party):
Melbourne Health

Study Description
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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.

Condition or disease Intervention/treatment Phase
Glioma Procedure: Biopsy Drug: Part A: AB-218 Procedure: Surgery (maximal resection) Drug: Part B: AB-218 Early Phase 1

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
Actual Study Start Date : October 11, 2022
Estimated Primary Completion Date : December 1, 2024
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: AB-218
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
 Procedure: Biopsy
Patients will undergo stereotactic biopsy by craniotomy or burr hole.

Drug: Part A: AB-218
Part A: AB-218 orally 250 mg BID for 28 days.

Procedure: Surgery (maximal resection)
Surgery: Maximal safe resection, within 24 hours of last dose of AB-218.

Drug: Part B: AB-218
Part B: AB-218 orally 250 mg BID for 28 days for up to 12 cycles.


Outcome Measures
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Primary Outcome Measures :
  1. Phase 0: Feasibility of Phase 0 study in patient population [ Time Frame: 14 months ]
    Number of patients to complete all planned investigations and procedures

  2. Phase 0: pharmacokinetic analysis of tumour tissue [ Time Frame: 4 weeks ]
    Total and unbound AB-218 in tumour tissue

  3. Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF) [ Time Frame: 4 weeks ]
    Total and unbound AB-218 in CSF

  4. Phase 2: Number of Adverse events [ Time Frame: up to 30 days after last study dose ]
    Number of adverse events (AEs) according to NCI CTCAE v 5

  5. Phase 2: Incidence of drug related adverse events [ Time Frame: up to 30 days after last study dose ]
    Drug related adverse events

  6. Phase 2: Incidence of dose limiting toxicity [ Time Frame: up to 30 days after last study dose ]
    Dose limiting toxicity events


Secondary Outcome Measures :
  1. Phase 0: Incidence of treatment emergent Adverse events [ Time Frame: during 1 cycle of AB-128, prior to maximal resection (4 weeks) ]
    Treatment emergent adverse events (AEs) according to NCI CTCAE v 5

  2. Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218 [ Time Frame: 30 days after maximal resection ]
    30-day morbidity and mortality post surgery

  3. Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour [ Time Frame: after maximal resection (4 weeks), at progression (optional) ]
    Changes in 2-hydroxyglutarate (2-HG) levels in tumour

  4. Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF) [ Time Frame: after maximal resection (4 weeks), at progression (optional) ]
    Changes in 2-hydroxyglutarate (2-HG) levels in cerebrospinal fluid (CSF)

  5. Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma [ Time Frame: after maximal resection (4 weeks), monthly during treatment, at progression (optional) ]
    Changes in 2-hydroxyglutarate (2-HG) levels in plasma

  6. Phase 0: anti-tumour activity [ Time Frame: 4 weeks ]
    Objective response (LGG RANO assessment)

  7. Phase 2: anti-tumour activity [ Time Frame: 8 weekly until progression ]
    Objective response (LGG RANO assessment)


Other Outcome Measures:
  1. Phase 2: Survival [ Time Frame: 30 days after last study dose ]
    Progression free survival (PFS)

  2. Phase 2: Survival [ Time Frame: 30 days after last study dose ]
    Overall survival (OS)

  3. Phase 2: Survival [ Time Frame: 30 days after last study dose ]
    Time to treatment failure (TTF)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients will have a radiological diagnosis of LGG or a previously confirmed LGG and be planned for elective, non-urgent resection of the tumour
  2. Patients who do not require urgent resection for mass effect, cerebral oedema or hydrocephalus in the opinion of the treating neurosurgeon
  3. Tumour size 2 - 5 cm
  4. Measurable and/or evaluable disease as per LGG-RANO criteria
  5. Willing to undergo planned surgical procedures

  6. Routine trial inclusion criteria

    1. Adults ≥ 18 < 40 years of age
    2. ECOG performance score 0 - 1
    3. Life expectancy of at least 24 months
    4. Haematological and renal function as prescribed
    5. Hepatic function with prescribed limits
    6. 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 urgent resection due to degree of mass effect, oedema, hydrocephalus or symptoms
  2. Patients who have received chemotherapy or radiation for the diagnosis of LGG
  3. Tumour involves cerebellum or brainstem

  4. Routine trial exclusion criteria

    1. Any significant Intracranial bleeding in the opinion of the principal investigator
    2. Prior malignancy
    3. Significant co-morbidity
    4. ECG abnormalities
    5. Recent surgery
    6. Known allergy or sensitivity to any of the excipients in the investigational product
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05577416


Contacts
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Contact: Kate Drummond, Prof +61 3 9345 2767 AnHeart@wehi.edu.au

Locations
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Australia, Victoria
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Kate Drummond         
Sponsors and Collaborators
Melbourne Health
Walter and Eliza Hall Institute of Medical Research
AnHeart Therapeutics Inc.
Investigators
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Principal Investigator: Kate Drummond, Prof Melbourne Health
More Information
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Responsible Party: Melbourne Health
ClinicalTrials.gov Identifier: NCT05577416    
Other Study ID Numbers: 2022.003
First Posted: October 13, 2022    Key Record Dates
Last Update Posted: October 13, 2022
Last Verified: October 2022

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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
Keywords provided by Melbourne Health:
IDH1
Diffuse Astrocytoma
oligodendroglioma
phase 0
perioperative
Additional relevant MeSH terms:
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Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue