A Trial of AMG 479, Everolimus (RAD001) and Panitumumab in Patients With Advanced Cancer - QUILT-3.007
Condition: Advanced Solid Tumors, Non-small Cell Lung Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1

Summary: 
      This open-label, non-randomized, dose escalation phase I biomarker trial of the triplet
      regimen of AMG 479, everolimus, and panitumumab for subjects with refractory advanced solid
      tumors is designed to assess the safety and tolerability of this combination as well as
      preliminary efficacy.
    

Detailed description: 
      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.

      Two sustained complete responses (one > 2 years of complete response, second >8 months of
      complete response) were seen in subjects with refractory NSCLC (never smokers) enrolled in
      the doublet regimen. Therefore, an additional 20 subjects with NSCLC, never smokers or
      non-smokers with ≤ 10 year pack smoking history will be enrolled at MTD/RPTD to further
      assess safety, tolerability and clinical activity in this specific patient cohort. In this
      cohort, subjects will start both drugs on cycle 1, day 1.

      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
      investigational drug.

      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), subependymal giant cell
      astrocytoma (a type of brain cancer), neuroendocrine tumors originating in the lung or
      gastrointestinal (GI) tract, and HER2-negative breast 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
      chemotherapy regimens.
    

Intervention name(s): AMG 479, Everolimus, Panitumumab
Intervention type(s): Drug
Intervention description(s): Dose Escalation Cohort #, Subjects, Everolimus, AMG 479
3-6 subjects, Study drug administered per dose level
3-6 subjects, Study drug administered per dose level
Expanded Cohort Subjects, Everolimus, AMG 479 20 subjects, study drug administered per dose level
Dose Escalation, Cohort #, Subjects, Everolimus, AMG 479, Panitumumab
3-6 subjects, Study drug administered per dose level
3-6 subjects, Study drug administered per dose level
Expanded Cohort Subjects, Everolimus, AMG 479, Panitumumab 20 subjects, Study drug administered per dose level
NSCLS Cohort Subjects, Everolimus, AMG 479, 20 subjects, Study drug administered per dose level
Intervention MeSH terms: Everolimus; Panitumumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Phase I; Solid Tumor; AMG 479; Panitumumab; Everolimus; RAD001; Duke; Subjects with refractory advanced solid tumors; non-small cell lung cancer