A Phase I Trial of the IGF-1R Antibody AMG 479 in Combination With Everolimus (RAD001) and Panitumumab in Patients With Advanced Cancer (The RAP Trial)
The purpose of this study is to find the safest dose of the drugs AMG 479 and everolimus in
combination and then with panitumumab added. This study will consist of two parts. If you
are enrolled in Part One of the study, you will receive AMG 479 and everolimus. If you are
enrolled in Part Two of the study, you will receive AMG 479, everolimus, and panitumumab.
The study will also look at how the drugs work in the body, and will see if there is any
effect on your cancer.
The study will have two parts: The first part will be to define the MTD/RPTD of the doublet
combination of AMG 479 + everolimus using a standard 3-6 subjects per dose level. Since
each agent is known to be well tolerated as monotherapy, we will start with the full dose of
AMG 479 and escalate the dose of everolimus. Once the RPTD is established, an additional 20
subjects will be added to confirm the tolerability of this regimen and to allow more
detailed biomarker assessment for the effect of each agent alone in the doublet combination.
In this biomarker expanded cohort, subjects will start treatment with 2 weeks of AMG 479
monotherapy (a single dose of AMG 479), followed by the combination of AMG 479 + everolimus
on day 15.
The second part of the study will assess tolerability of the triplet therapy, with
panitumumab added to the RPTD of AMG 479 + everolimus, again using a standard cohort size of
3-6 subjects. Finally, at the recommended phase II dose of the triplet therapy, 20 subjects
will be added to an expanded safety and biomarker cohort. In this biomarker expanded cohort,
10 subjects will start treatment with two weeks of AMG 479 monotherapy (a single dose of AMG
479), and 10 subjects will start treatment with two weeks of everolimus monotherapy, with
all subjects starting the triplet combination therapy with panitumumab on day 15.
ABOUT THE STUDY DRUGS:
AMG 479 is an intravenous (I.V., meaning through a vein) medication made from a special type
of human protein called antibodies. AMG 479 blocks the activity of another protein called
IGF-1R which is important for tumors to grow. Blocking IGFR-1 activity has been shown to
slow or kill cancer cells in laboratory studies. AMG 479 is currently being evaluated in
clinical research studies in a variety of cancers. AMG 479 is not approved by the U.S. Food
and Drug Administration (FDA) for the treatment of cancer and is therefore considered an
Everolimus is a pill that works by blocking the activity of a substance in the body known as
mTOR (mammalian target of rapamycin). mTOR is important for helping the growth and survival
in normal and cancer cells. Blocking mTOR activity has been shown to slow or kill cancer
cells in laboratory studies. Everolimus is currently being evaluated in clinical research
studies in a variety of cancers. Everolimus (AfinitorTM) is approved by the FDA for the
treatment of advanced renal cell carcinoma (kidney cancer). Besides cancer, everolimus also
has been tested for its ability to help block the rejection of solid organs transplants
(such as liver or kidney transplants). Everolimus is approved for this purpose in Europe
but not in the United States.
Panitumumab is another intravenous (I.V.) medication made from a special type of human
protein called antibodies. Panitumumab blocks the activity of a protein called EGFr which is
also important for tumors to grow. Blocking EGFr activity has been shown to slow or kill
cancer cells in laboratory studies. Panitumumab is currently being evaluated in clinical
research studies in a variety of cancers. Panitumumab (Vectibix™) is approved by the FDA
for the treatment of advanced colorectal cancer following 5'FU, oxaliplatin and irinotecan
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To define the maximal tolerated dose (MTD) and/or recommended phase II dose (RPTD) for the doublet AMG 479 in combination with everolimus in subjects with advanced solid tumors.
Gordana Vlahovic, MD
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|