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

Status: Recruiting
Phase:
Diagnosis: Solid Tumor/Phase I
NCT ID: NCT02073994 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 14-045

 

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 MTD. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Patrick Wen, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Jason Faris, MD, Massachusetts General Hospital

Contacts:
Dana-Farber Cancer Institute: Andrew Wolanski, 617-632-6623, andrew_wolanski@dfci.harvard.edu
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility 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 previously received AG-120. 2. Subjects who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration. 3. Subjects who received an investigational agent <14 days prior to their first day of study drug administration. 4. Subjects who are pregnant or breastfeeding. 5. 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). 6. 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. 7. Subjects with a history of myocardial infarction within the last 6 months. 8. Subjects with known unstable or uncontrolled angina pectoris. 9. Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias. 10. Subjects with heart-rate corrected QT (QTc) interval ≥450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events. 11. Subjects taking medications that are known to prolong the QT interval. 12. Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C. 13. 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.
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