Phase I Study of the Combination of Bevacizumab, Everolimus and LBH589 (BEL) for the Treatment of Advanced Solid Tumors
The main purpose of this study is to test the safety of three study drugs, bevacizumab
(Avastin™), Everolimus (Afinitor™) and LBH589 (Panobinostat) when they are given together.
It is hoped this study drug combination might lead to a greater decrease the in size of the
cancer and/or slow down how fast the cancer is growing compared to when these drugs are
There are two parts of the study.
The purpose of part I is to find out the highest and safest levels of these drugs when they
are given together. If you are enrolled in part I of the study, you will start all the study
drugs at the same time. The amount (dose) of drugs you will get will depend on when you
enter the study.
The purpose of part II is to see what effects, good and/or bad, the study drugs have when
they are given alone and together. In addition, this will also give us a better
understanding of how these study drugs work on you and your cancer. If you are enrolled in
part II of the study, you will enter one of three study drug arms:
Study Drug Arm A: You will receive everolimus alone for two weeks, then add bevacizumab and
LBH589 to your study regimen.
Study Drug Arm B: You will receive LBH589 alone for two weeks, then add bevacizumab and
LBH589 to your study regimen.
Study Drug Arm C: You will receive everolimus and LBH589 together for two weeks, then add
bevacizumab to your study regimen.
ABOUT THE STUDY DRUGS:
- Bevacizumab (Avastin™) is an intravenous (I.V., meaning through a vein) medication made
from a special type of human and mouse protein called antibodies. Bevacizumab blocks a
factor called VEGF (vascular endothelial growth factor) which is important for
angiogenesis (the growth of new blood vessels). Blocking this factor is thought to
block the growth of tumor-related blood vessels which may stop the growth of cancer.
Bevacizumab and other drugs that block VEGF activity are currently being evaluated in
clinical research studies in a variety of cancers.
- Everolimus (Afintor™) 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 and other drugs
that block mTOR activity are currently being evaluated in clinical research studies in
a variety of cancers.
- LBH589 (Panobinostat) is a new pill that works by blocking a special group of proteins
called histone deacetylases (HDACs). HDACs are important for helping the growth and
survival in normal and cancer cells and for helping the growth of new tumor-related
blood vessels. Blocking HDAC activity has been shown to shown to slow or kill cancer
cells in laboratory studies. LBH589 and other drugs that block HDACs activity are
currently being evaluated in clinical research studies in a variety of cancers. LBH589
(Panobinostat) is not approved by the U.S. Food and Drug Administration (FDA) for the
treatment of cancer is therefore considered an investigational drug.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To define the maximal tolerated dose (if any) and the recommended phase II dose for the triplet combination of everolimus plus LBH589 plus bevacizumab in subjects with advanced solid tumors
Herbert I Hurwitz, Md
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|