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

Glioma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03343197
• Other study ID #: AG120-881-C-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 20, 2018
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: May 2025
• Est. primary completion date: August 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• AG-120
Prior to surgery subjects will receive AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.
• AG881
Prior to surgery subjects will receive AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	United States, Massachusetts	Boston	Massachusetts
United States	United States, Texas	Dallas	Texas
United States	United States, North Carolina	Durham	North Carolina
United States	United States, California	Los Angeles	California
United States	United States, New York	New York	New York
United States	United States, California	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier

Country where clinical trial is conducted

United States, 

Outcome

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