Clinical Trial: Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T-cell Costimulatory Molecules (MVA-Brachyury-TRICOM)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label Phase I Study to Evaluate the Safety and Tolerability of a Modified Vaccinia Ankara (MVA) Based Vaccine Modified to Express Brachyury and T-Cell Costimulatory Molecules (MVA Brachyury-TR

Brief Summary:

Background:

- This cancer vaccine was developed to help teach the body's immune system to attack and destroy cancer cells. It teaches immune cells to target the Brachyury protein. This protein is present in some tumor cells, and it can help tumor cells spread to other parts of the body. Researchers want to see whether the new Brachyury protein vaccine can help treat people with advanced carcinomas.

Objective:

- To test the safety and effectiveness of giving the MVA-brachyury-TRICOM vaccine to people with cancer.

Eligibility:

- Adults ages 18 and over whose type of cancer has not responded to standard therapies who do not have a history of autoimmune diseases and are capable of taking care of themselves.

Design:

  • Participants will be screened with a medical history and physical exam. They will have blood and urine tests. They may have a computed tomography (CT) scan, a positron emission tomography (PET) scan, and a brain magnetic resonance imaging (MRI) scan. They may have a bone scan. They will have an electrocardiogram (ECG) to test heart rhythm.
  • Participants will have visits about every 4 weeks. They will have a physical exam and blood and urine tests. They will be injected with the vaccine under the skin into the upper thigh or around the armpits.
  • CT scans or MRI scans will be done at visit 1, after 3 months on study, and again 3 months later if still on the study. Another ECG will be done at their last vaccine visit.
  • When participants stop

    Detailed Summary:

    Background:

    • MVA-brachyury-TRICOM is a novel recombinant vector-based therapeutic cancer vaccine designed to induce an enhanced immune response against brachyury, which is overexpressed in many solid tumor types, such as lung, breast, ovarian, chordoma, prostate, colorectal, and pancreatic adenocarcinoma.
    • Modified vaccinia Ankara (MVA) is a replication-deficient, attenuated derivative of vaccinia. It is used in the smallpox vaccination and is now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer.
    • Many MVA vector-based trials conducted in patients with cancer have demonstrated its safety and the immunogenicity of its transgenes.
    • Brachyury is a member of the T-box family of transcription factors. It is overexpressed in cancer cells compared with normal tissue and has been linked to cancer cell resistance and metastatic potential.
    • Brachyury as a vaccine target has been demonstrated to be safe in an ongoing phase I study of recombinant yeast-brachyury and to generate brachyury-specific T-cell responses.
    • Poxviral vaccines delivering a triad of three human T-cell costimulatory molecules designated TRICOM (B7.1, ICAM-1 and LFA-3) have been extensively studied in both preclinical and clinical studies and have demonstrated their ability to induce robust T-cell activation and provide evidence of clinical benefit.
    • In vitro, MVA-brachyury-TRICOM is able to effectively expand brachyury-specific CD8+ and CD4+ T cells from peripheral blood mononuclear cells.
    • Previous work indicates that MVA-brachyury-TRICOM will induce activation a distinct Tcell subpopulation f
      Sponsor: National Cancer Institute (NCI)

      Current Primary Outcome: Safety and tolerability of escalating doses of MVA-brachyury-TRICOM vaccine. [ Time Frame: 2 -3 years ]

      Original Primary Outcome: Same as current

      Current Secondary Outcome:

      • CD8 and CD4 immunologic response as measured by an increase in brachyury-specific T cells. [ Time Frame: 2 -3 years ]
      • Evidence of clinical benefit, such as progression-free survival, RECIST criteria, reduction in serum markers, and/or reduction in circulating tumor cells. [ Time Frame: 2 -3 years ]
      • Frequency of immune cell subsets in peripheral blood and changes in serum levels of cytokines and antibodies to brachyury. [ Time Frame: 2 -3 years ]
      • Correlation of brachyury expression in tissue samples with clinical outcomes. [ Time Frame: 2 -3 years ]


      Original Secondary Outcome: Same as current

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: June 28, 2014
      Date Started: June 24, 2014
      Date Completion:
      Last Updated: May 12, 2017
      Last Verified: April 6, 2017