Open Label Study to Evaluate the Safety and Tolerability of GI-6301 a Vaccine Consisting of Whole Heat-Killed Recombitant Yeast Genetically Modified to Express Brachyury Protein in Adults With Solid Tumors

Inclusion Criteria:

• Patients must have histologically confirmed malignancy by the Laboratory of Pathology, NCI, that is metastatic or unresectable locally advanced malignant solid tumor. 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, or pancreatic).
• 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 ≥ 70).
• Age ≥ 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 disease-appropriate therapy for metastatic disease, or not be a candidate for therapy of proven efficacy for their disease.
• 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 GnRH agonist therapy (unless orchiectomy has been done).
• 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 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 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 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 spinal cord tumors or spinal cord metastasis due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.
• Patients with pericardial masses >1 cm will be excluded.
• Concurrent chemotherapy.
• 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.
• History of previous autoimmune thyroiditis as defined by a positive anti-Thyroid Peroxidase (TPO) antibody screen.
• Patients with grade 3 hypothyroidism or hyperthyroidism.
• Patients with clinically concerning thyroid nodules found on screening exam.
• Patients within one year of acute Epstein-Barr Virus (EBV) infection or patients known to have EBV viremia.