Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors
I. To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479
(ganitumab) and RAD001 (everolimus) in patients with refractory solid tumors.
II. To determine the safety and toxicity of AMG479 and RAD001.
I. To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors:
response and stable disease rates, duration of response and of stable disease, time to
progression (TTP) and overall survival (OS).
II. For all patients, to analyze tumor and blood samples for pharmacodynamic biomarkers
related to IGF-1R and mTOR signaling: pAkt, pS6, p-4EBP1, PTEN, IGF-1, IGF-2, pIGF-1R and
IGFBP3 and correlate with response and stable disease.
III. For all patients, to analyze the pharmacokinetic profile (PK) for RAD001 and AMG479,
and correlate with response/stable disease and pharmacodynamic markers.
IV. To evaluate the effects of RAD001 on AMG 479 pharmacokinetics.
OUTLINE: This is a dose-escalation study.
Patients receive everolimus orally (PO) once daily (QD) on days 1-28 (days 1-7 and 16-28 of
course 1 only) and ganitumab intravenously (IV) over 60 minutes on days 1 and 15 (day 15 of
course 1 only). Courses repeat every 28 days in the absence of disease progression or
After completion of study treatment, patients are followed up at day 30, every 3 months for
2 years from registration for study treatment, every 6 months for years 3-5, and then
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors
Shadia I Jalal, MD
Indiana University Melvin and Bren Simon Cancer Center
United States: Food and Drug Administration
|Indiana University Melvin and Bren Simon Cancer Center||Indianapolis, Indiana 46202-5289|