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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

Tracking Information
First Submitted Date  ICMJE September 19, 2022
First Posted Date  ICMJE October 13, 2022
Last Update Posted Date October 13, 2022
Actual Study Start Date  ICMJE October 11, 2022
Estimated Primary Completion Date December 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2022)
  • Phase 0: Feasibility of Phase 0 study in patient population [ Time Frame: 14 months ]
    Number of patients to complete all planned investigations and procedures
  • Phase 0: pharmacokinetic analysis of tumour tissue [ Time Frame: 4 weeks ]
    Total and unbound AB-218 in tumour tissue
  • Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF) [ Time Frame: 4 weeks ]
    Total and unbound AB-218 in CSF
  • 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
  • Phase 2: Incidence of drug related adverse events [ Time Frame: up to 30 days after last study dose ]
    Drug related adverse events
  • Phase 2: Incidence of dose limiting toxicity [ Time Frame: up to 30 days after last study dose ]
    Dose limiting toxicity events
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2022)
  • 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
  • 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
  • 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
  • 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)
  • 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
  • Phase 0: anti-tumour activity [ Time Frame: 4 weeks ]
    Objective response (LGG RANO assessment)
  • Phase 2: anti-tumour activity [ Time Frame: 8 weekly until progression ]
    Objective response (LGG RANO assessment)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 11, 2022)
  • Phase 2: Survival [ Time Frame: 30 days after last study dose ]
    Progression free survival (PFS)
  • Phase 2: Survival [ Time Frame: 30 days after last study dose ]
    Overall survival (OS)
  • Phase 2: Survival [ Time Frame: 30 days after last study dose ]
    Time to treatment failure (TTF)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
Official Title  ICMJE A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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
Condition  ICMJE Glioma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: AB-218
Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)
Interventions:
  • Procedure: Biopsy
  • Drug: Part A: AB-218
  • Procedure: Surgery (maximal resection)
  • Drug: Part B: AB-218
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 11, 2022)		 10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2025
Estimated Primary Completion Date December 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kate Drummond, Prof +61 3 9345 2767 AnHeart@wehi.edu.au
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05577416
Other Study ID Numbers  ICMJE 2022.003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Melbourne Health
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Melbourne Health
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Walter and Eliza Hall Institute of Medical Research
  • AnHeart Therapeutics Inc.
Investigators  ICMJE
Principal Investigator: Kate Drummond, Prof Melbourne Health
PRS Account Melbourne Health
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP