Clinical trial NCT03343197: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioma
Keywords: Glioma
IDH1
AG-120
AG-881
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

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).

Primary outcomes:
measure: 2-HG concentration in surgically resected tumors
timeFrame: Up to 4 weeks, on average
Secondary outcomes:
measure: Safety and tolerability: incidence of adverse events and serious adverse events
timeFrame: Up to 48 weeks, on average
measure: Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.
timeFrame: Up to 4 weeks, on average
measure: Peak Plasma Concentration (Cmax) of AG-120 or AG-881
timeFrame: Up to 4 weeks, on average
measure: Time to maximum concentration (Tmax) of AG-120 or AG-881
timeFrame: Up to 4 weeks, on average
measure: Area Under the Curve (AUC) of AG-120 or AG-881
timeFrame: Up to 4 weeks, on average
measure: Elimination half-life of AG-120 or AG-881
timeFrame: Up to 4 weeks, on average
measure: Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.
timeFrame: Up to 48 weeks, on average
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: United States, California
state: California
city: San Francisco
country: United States
facility: United States, California
state: California
city: Boston
country: United States
facility: United States, Massachusetts
state: Massachusetts
city: New York
country: United States
facility: United States, New York
state: New York
city: Durham
country: United States
facility: United States, North Carolina
state: North Carolina
city: Dallas
country: United States
facility: United States, Texas
state: Texas
Study officials:
References:
citation: Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF. Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023 Mar;29(3):615-622. doi: 10.1038/s41591-022-02141-2. Epub 2023 Feb 23.