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Trial record 1 of 1 for:    AG120-881-C-001
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Study of AG-120 and AG-881 in Subjects With Low Grade Glioma

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03343197
Recruitment Status : Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : August 24, 2021
Sponsor:
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

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.

Condition or disease Intervention/treatment Phase
Glioma Drug: AG-120 Drug: AG881 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 20, 2018
Actual Primary Completion Date : August 2, 2019
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Ivosidenib

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. 2-HG concentration in surgically resected tumors [ Time Frame: Up to 4 weeks, on average ]

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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03343197


Locations
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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
Institut de Recherches Internationales Servier
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT03343197    
Other Study ID Numbers: AG120-881-C-001
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: August 24, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

  • used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

  • sponsored by Servier
  • with a first patient enrolled as of 1 January 2004 onwards
  • for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL: https://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
Glioma
IDH1
AG-120
AG-881
Additional relevant MeSH terms:
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Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Ivosidenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action