Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Agios Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02073994
First received: February 21, 2014
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced solid tumors, including glioma, that harbor an IDH1 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where three cohorts of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Cholangiocarcinoma
Chondrosarcoma
Glioma
Advanced Solid Tumors
Drug: AG-120
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation

Resource links provided by NLM:


Further study details as provided by Agios Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety/tolerability: incidence of adverse events [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose and/or the recommended Phase II dose of AG-120 in subjects with advanced solid tumors, including glioma [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose Limiting Toxicities of AG-120 in subjects with advanced solid tumors, including glioma [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of AG-120 in subjects with advanced solid tumors, including glioma [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
    Descriptive statistics will be used to summarize PK parameters for each dose group and, where appropriate, for the entire population. Such parameters will include max concentration (Cmax), time to maximum concentration (Tmax), AUC, elimination half-life.

  • Pharmacodynamic relationship of AG-120 and 2-HG [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]

    PD parameters will be summarized using the following descriptive statistics: n, Mean, SD, CV%, Median, Min, and Max, GeoMean, and GeoCV%.

    PK/PD correlations between exposure to AG-120 and the extent of suppression of 2-HG will be explored using graphical display of data.


  • Clinical Activity associated with AG-120 in subjects with advanced solid tumors, including glioma [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
    The clinical activity of AG-120 will be evaluated by assessing response to treatment according to RECIST v1.1 for subjects without glioma or by modified RANO criteria for subjects with glioma


Estimated Enrollment: 51
Study Start Date: March 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
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. Subjects may continue treatment with AG-120 until disease progression or development of other unacceptable toxicity.
Drug: AG-120
AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AG-120 until disease progression or development of other unacceptable toxicity

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Subject must be ≥18 years of age.
  2. Subjects must have histologically or cytologically confirmed advanced solid tumors, including glioma, that have recurred or progressed following standard therapy, or that have not responded to standard therapy.
  3. Subjects must have documented IDH1 gene-mutated disease based on local test evaluation.
  4. Subject must have evaluable disease by RECIST v1.1 for subjects without glioma or by RANO criteria for subjects with glioma.
  5. Subjects must be amenable to serial peripheral blood sampling, urine sampling, and biopsies during the study.
  6. Subjects must have ECOG PS of 0 to 1.
  7. Subjects must have expected survival of ≥3 months.
  8. Subjects must have adequate bone marrow function as evidenced by absolute neutrophil count ≥1.5 ×10^9/L; Hemoglobin >9 g/dL (Subjects are allowed to be transfused to this level); Platelets ≥75 × 10^9/L
  9. Subjects must have adequate hepatic function as evidenced by Serum total bilirubin ≤1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement; Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤2.5 × ULN. For subjects with bone metastases and/or suspected disease-related liver or biliary involvement, ALP must be ≤5 × ULN.
  10. Subjects must have adequate renal function as evidenced by Serum creatinine ≤2.0 × ULN OR Creatinine clearance >40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR)
  11. Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
  12. Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Subjects with reproductive potential are defined as one who is biologically capable of becoming pregnant. Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days (females and males) following the last dose of AG-120.

Key Exclusion Criteria:

  1. Subjects who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration.
  2. Subjects who received an investigational agent <14 days prior to their first day of study drug administration.
  3. Subjects who are pregnant or breastfeeding.
  4. Subjects with an active severe infection or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
  5. Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1.
  6. Subjects with a history of myocardial infarction within the last 6 months.
  7. Subjects with known unstable or uncontrolled angina pectoris.
  8. Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
  9. Subjects with heart-rate corrected QT (QTc) interval ≥450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events.
  10. Subjects taking medications that are known to prolong the QT interval.
  11. Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
  12. Subjects with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including those used to control symptoms, within 2 months of randomization. Subjects with glioma who are on a stable, steroid-dosing regimen prior to screening MRI may be permitted to enroll with Medical Monitor approval.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02073994

Contacts
Contact: Molly Prahl, RN 617.649.8635 molly.prahl@agios.com
Contact: Sam Agresta, MD, MPH & TM 617.649.8621 sam.agresta@agios.com

Locations
United States, Arizona
Recruiting
Scottsdale, Arizona, United States, 85255
United States, California
Recruiting
Los Angeles, California, United States, 90095
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Not yet recruiting
Miami, Florida, United States, 33136
United States, Maryland
Not yet recruiting
Baltimore, Maryland, United States, 21218
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Recruiting
New York, New York, United States, 10065
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Dallas, Texas, United States, 75390
Recruiting
San Antonio, Texas, United States, 78229
France
Recruiting
Villejuif, France, 94800
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
Study Director: Clinical Development Agios Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02073994     History of Changes
Other Study ID Numbers: AG120-C-002
Study First Received: February 21, 2014
Last Updated: October 8, 2014
Health Authority: United States: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM)

Keywords provided by Agios Pharmaceuticals, Inc.:
chondrosarcoma
cholangiocarcinoma
glioma
advanced solid tumors
IDH1
AG-120

Additional relevant MeSH terms:
Cholangiocarcinoma
Chondrosarcoma
Glioma
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Sarcoma

ClinicalTrials.gov processed this record on October 20, 2014