BN Brachyury and Radiation in Chordoma
Condition: Chordoma
MeSH terms: Chordoma
Intervention: BN-Brachyury plus radiation
Intervention description: MVA-BN-Brachyury injections will be given on day 0 and 14. FPV-Brachyury injection will be given on day 28, followed by radiation on days 42 through approximately day 70. FPV-Brachyury will then be given two weeks after radiation then every 6-12 weeks through 110 weeks after radiation is complete.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 12 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      The goal of this study is to determine if the combination of BN-Brachyury plus radiation
      therapy can induce objective radiographic response rate (ORR) in patients, using a Simon
      2-stage optimal design. In stage 1, a minimum of threshold of activity is needed to proceed
      to stage 2.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed chordoma

          -  Patients must have measurable disease by RECIST 1.1

          -  Patients must be scheduled to have radiation therapy to at least 1 target lesion.

          -  Age ≥12 years

          -  Patients must have normal organ and marrow function

          -  Must have recovered completely from any reversible toxicity associated with recent
             therapy.

          -  There should be a minimum of 2 weeks from any chemotherapy, small molecule/targeted
             therapy, immunotherapy and/or radiation prior to enrolment

          -  Females of childbearing potential and male partners of Females of childbearing
             potential must agree to use effective birth control or abstinence from screening to
             after the last vaccination therapy

        Exclusion Criteria:

          -  Concurrent treatment for cancer, with specific exceptions noted in the inclusion
             criteria

          -  Chronic hepatitis B or C infection.

          -  Any significant disease, that in the opinion of the investigator may impair the
             patient's tolerance of trial treatment.

          -  Significant dementia, altered mental status, or any psychiatric condition that would
             prohibit the understanding, or rendering of informed consent.

          -  Active autoimmune diseases requiring treatment or a history of autoimmune disease that
             might be stimulated by vaccine treatment. This requirement is due to the potential
             risks of exacerbating autoimmunity.

          -  Concurrent use of systemic steroids, except for physiological doses of systemic
             steroid replacement or local steroid use.

          -  Patients who are receiving any other investigational agents within 28 days before
             start of trial treatment.

          -  History of allergic reactions attributed to compounds of similar chemical or
             biological composition to MVA-BN/FPV-Brachyury or other agents used in trial. History
             of allergic reactions to aminoglycoside antibiotic or egg products.

          -  Serious or uncontrolled intercurrent illness, included but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia or psychiatric illness/social situations that, in the opinion of
             the investigator, would limit compliance with trial requirements.

          -  Pregnant women are excluded from this trial due to the unknown effects of the
             BN-Brachyury on the fetus or infant.

          -  HIV-positive patients are ineligible because of the potential for decreased immune
             response to the vaccine.

          -  Significant cardiovascular disease, which includes but is not limited to New York
             Heart Association Heart Failure Class II or greater, myocardial infarction within the
             previous 3 months, unstable arrhythmias, unstable angina.