Cancer Vaccine Targeting Brachyury Protein in Tumors
Condition: Neoplasms; Malignant Solid Tumors; Colon Neoplasms; Adenocarcinoma
MeSH terms: Neoplasms; Colonic Neoplasms
Intervention: GI-6301 (Yeast Brachyury Vaccine)
Intervention description: GI-6301 is a heat-killed, recombinant yeast-based vaccine engineered to express the transcription factor, Brachyury. The Brachyury gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wildtype yeast) to produce the final recombinant vaccine product.
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Vaccine Therapy; Dose-Limiting Toxicity; Maximum Tolerated Dose; Clinical Response; Immune Response; Cancer; Solid Tumor

Summary:

      Background:

      - Cancer vaccines are being developed to help teach the body's immune system to attack and
      destroy cancer cells. A new vaccine being tested targets 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.

      Objectives:

      - To test the safety and effectiveness of a cancer vaccine that targets Brachyury protein in
      tumor cells.

      Eligibility:

        -  Individuals at least 18 years of age who have advanced cancers that have not responded
           or are no longer responding to standard treatments.

        -  Because the vaccine is made with yeast, people with yeast allergies will not be
           eligible.

      Design:

        -  Participants will be screened with a medical history and physical exam. Imaging studies
           will be used to examine the cancer. Heart and thyroid function tests will be conducted.
           Blood and urine samples will also be collected.

        -  Participants will receive vaccine injections every 2 weeks, for a total of seven visits.
           After seven visits, if the cancer has shrunk or stopped growing, participants will
           continue to have the vaccine about once a month.

        -  Treatment will be monitored with frequent blood tests and imaging studies. Other tests
           will be given as directed by the study doctors. Some participants will have apheresis to
           collect additional blood cells for study.

        -  Participants will continue to receive the vaccine as long the tumor does not start
           growing again and there are no serious side effects....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Participants must meet the following criteria for participation:

          -  Diagnosis: Patients must have histologically confirmed malignancy by the Laboratory of
             Pathology, National Cancer Institute (NCI), that is metastatic or unresectable locally
             advanced malignant solid tumor. In the case of Chordoma, unresectable, locally
             recurrent, or metastatic tumors are acceptable for enrollment, given that this
             represents incurable disease. Efforts will be made, as much as possible, to enroll
             patients with tumor types with known increased expression of Brachyury (such as lung,
             breast, ovarian, prostate, colorectal, pancreatic, or chordoma).

          -  Patients may have disease that is measurable or non-measurable but evaluable disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry
             (Karnofsky greater than or equal to 70)

          -  Age greater than or equal to 18 years. Because no dosing or adverse event data are
             currently available on the use of Yeast Brachyury vaccine in patients <18 years of
             age, children are excluded from this study, but will be eligible for future pediatric
             trials.

          -  Prior Therapy: Completed or had disease progression on at least one prior line of
             diseaseappropriate therapy for metastatic disease, or not be a candidate for therapy
             of proven efficacy for their disease.

          -  Patients must have normal organ and marrow function as defined below:

               -  Serum creatinine 1.5 times upper limit of normal OR creatinine clearance on a
                  24-h urine collection of 60 mL/min.

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 times the
                  upper limits of normal.

               -  Total bilirubin less than or equal to 1.5 times upper limit of normal OR in
                  patients with Gilbert's syndrome, a total bilirubin 3.0.

               -  Hematological eligibility parameters (within16 days of starting therapy):

               -  Granulocyte count 1,500/mm(3)

               -  Platelet count 100,000/m(3)

               -  Patients must have baseline pulse oximetry > 90% on room air.

          -  Recovered completely (Grade 1 or baseline) from any reversible toxicity associated
             with recent therapy. Typically this is 3 4 weeks for patients who most recently
             received cytotoxic therapy, except for the nitrosoureas and mitomycin C for which 6
             weeks is needed for recovery.

          -  There should be a minimum of 2 weeks from any prior chemotherapy, immunotherapy and/or
             radiation.

          -  Prior immune therapy is allowed.

          -  Men and women of child-bearing potential must agree to use effective birth control or
             abstinence during and for a period of 4 months after the last vaccination therapy.

          -  Patients with prostate cancer must continue to receive gonadotropin-releasing hormone
             (GnRH) agonist therapy (unless orchiectomy has been done). If a patient has refused
             GnRH therapy, they may be enrolled on a dose level for which the safety has already
             been determined.

          -  Patients with estrogen-receptor positive (ER+) breast cancer being treated with
             adjuvant hormonal therapy (selective estrogen receptor modulator or aromatase
             inhibitor) who have rising tumor markers as evidence of disease progression or
             metastatic disease on scans may continue on hormonal therapy while being treated with
             vaccine.

          -  Patients must be negative for yeast allergy skin test

          -  Ability to understand and the willingness to sign a written informed consent document.

        EXCLUSION CRITERIA:

        Patients with any of the following will not be eligible for participation in this study:

        - Patients should have no evidence of immune dysfunction as listed below.

          -  Human immunodeficiency virus (HIV) positivity due to the potential for decreased
             immune response to the vaccine.

          -  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. However, patients with vitiligo, diabetes
             mellitus, and hashimoto s thyroiditis on appropriate replacement therapy may be

        enrolled.

        --Concurrent use of systemic steroids, except for physiologic doses of systemic steroid
        replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic
        steroids (e.g., in patients with exacerbations of reactive airway disease or to prevent
        intravenous (IV) contrast allergic reaction or anaphylaxis in patients who have known
        contrast allergies) are allowed.

          -  History of allergy or untoward reaction to yeast-based products (any hypersensitivity
             to yeast-based products will be excluded).

          -  Pregnant or breast-feeding women, due to the unknown effects of the Yeast Brachyury
             vaccine on the fetus or infant.

          -  Serious intercurrent medical illness which would interfere with the ability of the
             patient to carry out the treatment program, including, but not limited to,
             inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active
             diverticulitis.

          -  Untreated brain metastases (or local treatment of brain metastases within the last 6
             months) and or spinal cord metastasis.

          -  Patients with pericardial masses >1 cm will be excluded.

          -  Concurrent chemotherapy. (However, the following anti-tumor therapies will be allowed:
             Trastuzumab for human epidermal growth factor receptor 2 (HER2+) breast cancer and
             hormonal therapy for breast (e.g., selective estrogen receptor modulators, aromatase
             inhibitors) and prostate cancer (e.g., GnRH antagonists/agonists or antagonists and
             androgen receptor antagonists).

          -  Chronic hepatitis infection, including B and C, because potential immune impairment
             caused by these disorders may diminish the effectiveness of this immunologic therapy.

          -  Patients requiring continuous tricyclic antidepressant therapy should be excluded due
             to the interference with the yeast skin test in creating false negative test results.

          -  Participation in another interventional clinical trial within 28 days before start of
             study treatment.

          -  Any significant disease that, in the opinion of the investigator, may impair the
             patient s tolerance of study treatment.

          -  Significant dementia, altered mental status, or any psychiatric condition that would
             prohibit the understanding or rendering of informed consent.