Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors
The purpose of this study is to test the safety of the combination of two drugs called RAD001 and AMG479. This study will see what effects (good and bad) RAD001 and AMG479 have on cancer. This study will also find the highest doses of RAD001 and AMG479 that can be given without causing severe side effects.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors|
- To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- To evaluate the grade and severity of adverse events as a measure of safety and toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors [ Time Frame: 5-10 years ] [ Designated as safety issue: No ]response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS)
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||December 2016|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Open Label
Drug: RAD001 + AMG479
Escalating doses of RAD001 + AMG479. Starting cohort will be 5 mg RAD001 once daily, continuous + AMG479 12 mg/kg on Day 1 and 15 of each 28 day cycle.
Other Name: everolimus + ganitumab
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 unacceptable toxicity.
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 annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01122199
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|Study Chair:||Shadia I Jalal, MD||Indiana University Melvin and Bren Simon Cancer Center|