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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

Phase 1
18 Years
Open (Enrolling)
Solid Tumors

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Trial Information

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

This is an open label, phase I trial with sequential cohorts of patients (3-6 patients per
dose cohort) with dose escalation of a heat-killed Yeast-Brachyury vaccine. Yeast-Brachyury
vaccine will be administered subcutaneously at 4 sites on 7 visits (Days 1, 15, 29, 43, 57,
71, 85 all +/- 2 days), then monthly until patients meet off-treatment criteria. The first
3 treatment cycles will consist of 2 vaccines and will last 28 days each; subsequent cycles
will consist of one monthly vaccine treatment. Restaging of disease will be performed after
the initial 3 cycles and then every 2 cycles thereafter.

For the first three patients on each dose level, there will be staggered enrollment of at
least 2 weeks between patients.

Dose levels and responses to a vaccine are very different to drugs so we have no way of
knowing a priori if a lower dose will result in more of a therapeutic anti-tumor immune
response than a higher dose. Thus, up to 6 patients may be enrolled on each dose level in
order to gain further information about safety and immunogenicity, providing that the
maximally tolerated dose has not been exceeded.

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, 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
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 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

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,
diabetes mellitus, and hashimoto's thryoiditis 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 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
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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Adverse events of escalating doses of GI-6301 vaccine

Outcome Description:

Type and Grade of treatment emergent adverse events.

Outcome Time Frame:

At end of treatment (36 months)

Safety Issue:


Principal Investigator

James L Gulley, M.D. Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

January 2012

Completion Date:

June 2014

Related Keywords:

  • Solid Tumors
  • Solid Tumors
  • Brachyury
  • Lung cancer
  • Breast cancer
  • Ovarian cancer
  • Prostate cancer
  • Colorectal cancer
  • Pancreatic cancer
  • Chordoma
  • Neoplasms



NCI, CCR Bethesda, Maryland  20892