Clinical Trial - NCT03343197

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

Recruiting

Sponsor: Agios Pharmaceuticals, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03343197

Protocol Info

Short Description: Phase 1 Study of AG-120 and AG-881 in Subjects With Low Grade Glioma
Long Description: 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
MGH Status: Open
Sponsor: Agios Pharmaceuticals
Disease Program: Brain/CNS

Next Steps


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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.
Condition Title Intervention Phase
Glioma AG-120 AG881 Phase 1
Study Type Interventional
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

Primary Outcome Measures

2-HG concentration in surgically resected tumors [Time Frame: Up to 4 weeks, on average] [Designated as safety issue: ]


Secondary Outcome Measures

Safety and tolerability: incidence of adverse events and serious adverse events [Time Frame: Up to 48 weeks, on average] [Designated as safety issue: ]

Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma. [Time Frame: Up to 4 weeks, on average] [Designated as safety issue: ]

Peak Plasma Concentration (Cmax) of AG-120 or AG-881 [Time Frame: Up to 4 weeks, on average] [Designated as safety issue: ]

Time to maximum concentration (Tmax) of AG-120 or AG-881 [Time Frame: Up to 4 weeks, on average] [Designated as safety issue: ]

Area Under the Curve (AUC) of AG-120 or AG-881 [Time Frame: Up to 4 weeks, on average] [Designated as safety issue: ]

Elimination half-life of AG-120 or AG-881 [Time Frame: Up to 4 weeks, on average] [Designated as safety issue: ]

Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria. [Time Frame: Up to 48 weeks, on average] [Designated as safety issue: ]

Estimated Enrollment: 45
Study Start Date: March 2018
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2020
Arms Assigned Interventions

Experimental:AG-120

AG-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 .
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.

Experimental:AG-881

AG-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.
Drug: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.

No Intervention:No Treatment Pre-Surgery

Subjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03343197

Locations

  • United States, California
    • United States, California Los Angeles, California, United States, 90024
    • United States, California San Francisco, California, United States, 94143
  • United States, Massachusetts
    • United States, Massachusetts Boston, Massachusetts, United States, 02215
  • United States, New York
    • United States, New York New York, New York, United States, 10065
  • United States, North Carolina
    • United States, North Carolina Durham, North Carolina, United States, 27710
  • United States, Texas
    • United States, Texas Dallas, Texas, United States, 75390

Sponsors and Collaborators

Agios Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03343197
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Agios Pharmaceuticals, Inc.:

Glioma

IDH1

AG-120

AG-881

Additional relevant MeSH terms:

Glioma

Ivosidenib

Glycine

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019