An Open Label Phase 1 Study to Evaluate the Safety and Tolerability of GI-6301 a Vaccine Consisting of Whole Heat-Killed Recombitant Saccharomyces Cerevisiae Yeast Genetically Modified to Express Brachyury Protein in Adults With Solid Tumors
- 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, 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 ≥ 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
- 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 with ER+ breast cancer being treated with adjuvant hormonal therapy
(selective estrogen receptor modulator or aromatase inhibitor) but have rising tumor
markers as evidence of disease progression 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
- 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 thryoiditis on appropriate replacement therapy may
- 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
- 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.
- 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
- 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.