Clinical Trials /

Study of AG-120 and AG-881 in Subjects With Low Grade Glioma

NCT03343197

Description:

Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.

Related Conditions:
  • Astrocytoma
  • Oligodendroglioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AG-120 and AG-881 in Subjects With Low Grade Glioma
  • Official Title: A Phase 1, Multicenter, Randomized, Controlled, Open-Label, Perioperative Study of AG-120 and AG-881 in Subjects With Recurrent, Non-Enhancing, IDH1 Mutant, Low Grade Glioma

Clinical Trial IDs

  • ORG STUDY ID: AG120-881-C-001
  • NCT ID: NCT03343197

Conditions

  • Glioma

Interventions

DrugSynonymsArms
AG-120AG-120
AG881AG-881

Purpose

Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.

Detailed Description

      A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for
      patients who require surgery. The purpose of this study is to evaluate the suppression of
      2-HG by comparing the concentration of 2-HG in resected tumors from IDH1 mutant glioma
      subjects following AG-120 or AG-881 treatment with the 2-HG concentration in untreated,
      control tumors. The safety, tolerability, PK/PD, and anti tumor activity data from the study
      in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom
      surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for
      future studies in glioma.
    

Trial Arms

NameTypeDescriptionInterventions
AG-120ExperimentalAG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 .
  • AG-120
AG-881ExperimentalAG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-881.
  • AG881
No Treatment Pre-SurgeryNo InterventionSubjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Be ≥18 years of age.
    
              2. Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG
                 (oligodendroglioma or astrocytoma according to World Health Organization 2016
                 classification).
    
              3. Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX
                 mutation status by local testing.
    
              4. Have central confirmation of primarily non-enhancing disease by MRI with less than or
                 equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted
                 image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring
                 1×1×1 cm.
    
              5. Be candidates for clinical resection but for whom surgery is not urgently indicated
                 (eg, for whom surgery within the next 2-4 months is appropriate).
    
              6. Have KPS of ≥60%
    
              7. Have expected survival of ≥12 months.
    
            Exclusion Criteria:
    
              1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of
                 AG-120 or AG-881 or have received an investigational agent <14 days prior to their
                 first dose of AG-120 or AG-881. In addition, the first dose of AG-120 or AG-881 should
                 not occur before a period of ≥5 half-lives of the investigational agent has elapsed.
    
              2. Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior
                 biopsy or surgery is allowed.)
    
              3. Have received any prior treatment with an IDH inhibitor.
    
              4. Have received any prior treatment with bevacizumab (Avastin).
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:2-HG concentration in surgically resected tumors
    Time Frame:Up to 4 weeks, on average
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Safety and tolerability: incidence of adverse events and serious adverse events
    Time Frame:Up to 48 weeks, on average
    Safety Issue:
    Description:
    Measure:Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.
    Time Frame:Up to 4 weeks, on average
    Safety Issue:
    Description:
    Measure:Peak Plasma Concentration (Cmax) of AG-120 or AG-881
    Time Frame:Up to 4 weeks, on average
    Safety Issue:
    Description:
    Measure:Time to maximum concentration (Tmax) of AG-120 or AG-881
    Time Frame:Up to 4 weeks, on average
    Safety Issue:
    Description:
    Measure:Area Under the Curve (AUC) of AG-120 or AG-881
    Time Frame:Up to 4 weeks, on average
    Safety Issue:
    Description:
    Measure:Elimination half-life of AG-120 or AG-881
    Time Frame:Up to 4 weeks, on average
    Safety Issue:
    Description:
    Measure:Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.
    Time Frame:Up to 48 weeks, on average
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Agios Pharmaceuticals, Inc.

    Trial Keywords

    • Glioma
    • IDH1
    • AG-120
    • AG-881

    Last Updated

    November 9, 2017