Safety Study of Bevacizumab, Everolimus and LBH589 (BEL) for Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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 given
      alone.

      Subjects will be enrolled at Duke University Medical Center (DUMC).
    

Detailed description: 
      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 given
      alone.

      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.
    

Intervention name(s): Bevacizumab, Everolimus and LBH589
Intervention type(s): Drug
Intervention description(s): Dose Escalation Cohort #, Subjects, Bevacizumab, Everolimus, LBH589
3-6, All study drugs administered per dose level
3-6, All study drugs administered per dose level
3-6, All study drugs administered per dose level
Expanded Cohorts Cohort #, Subjects, Bevacizumab, Everolimus, LBH589 A, B & C; 30, Recommended Phase II Dose for all three compounds
Intervention MeSH terms: Bevacizumab; Everolimus; Panobinostat
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment