Open Label Study to Evaluate the Safety and Tolerability of GI-6301 (Whole Heat-Killed Recombinant Yeast Modified to Express Brachyury Protein) in Adults With Solid Tumors

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
GlobeImmune Identifier:
First received: January 12, 2012
Last updated: August 25, 2015
Last verified: August 2015

This is an open label, phase I trial with sequential dose escalation cohorts of patients (3-6 patients per dose cohort) for 4 doses of GI-6301 (Yeast-Brachyury vaccine).

GI-6301 (Yeast-Brachyury vaccine) will be administered subcutaneously at 4 sites biweekly for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly until patients meet off-study criteria.

All patients on a given dose level will have completed 28 days on-study without dose limiting toxicities (DLT) before enrollment can begin on the next dose level or on the expansion phase.

Expansion Phase: 10 additional patients will be enrolled in the third dose group, receiving the same treatment regimen, to assess for immunologic responses and clinical responses. An additional 10 patients will be enrolled in the fourth dose group. Up to 38 patients may be theoretically required to complete this trial.

Condition Intervention Phase
Solid Tumors
Biological: GI-6301
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase 1 Study to Evaluate the Safety and Tolerability of GI-6301 a Vaccine Consisting of Whole Heat-Killed Recombinant Saccharomyces Cerevisiae Yeast Genetically Modified to Express Brachyury Protein in Adults With Solid Tumors

Resource links provided by NLM:

Further study details as provided by GlobeImmune:

Primary Outcome Measures:
  • Adverse events of escalating doses of GI-6301 vaccine [ Time Frame: At end of treatment (36 months) ] [ Designated as safety issue: Yes ]
    Type and Grade of treatment emergent adverse events.

  • Change in T cell precursors [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Determine in an expanded cohort if a significant change in T cell precursors will be detectable as measured by an increase in Brachyury-specific T cell ELISPOT assay and proliferation.

Secondary Outcome Measures:
  • Clinical Benefit [ Time Frame: At the end of treatment (36 months) ] [ Designated as safety issue: No ]
    To evaluate evidence of clinical benefit, such as progression-free survival, clinical radiographic response, reduction in serum markers, and/or reduction in circulating tumor cells.

  • General immune activation [ Time Frame: At the end of treatment (36 months) ] [ Designated as safety issue: No ]
    To evaluate parameters of general immune activation: Frequency of immune cell subsets in peripheral blood and changes in serum levels of cytokines.

Enrollment: 34
Study Start Date: January 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GI-6301 Vaccine Arm
Escalating dose groups of 3-6 subjects to receive 4YU and 16YU; 13 subjects to receive 40YU and 10 subjects to receive 80YU.
Biological: GI-6301
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 to produce the final recombinant vaccine product.

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 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, 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 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01519817

United States, Maryland
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: James L Gulley, M.D. Ph.D. LTIB, CCR, NCI
  More Information

No publications provided

Responsible Party: GlobeImmune Identifier: NCT01519817     History of Changes
Other Study ID Numbers: GI-6301-01
Study First Received: January 12, 2012
Last Updated: August 25, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by GlobeImmune:
Solid Tumors
Lung cancer
Breast cancer
Ovarian cancer
Prostate cancer
Colorectal cancer
Pancreatic cancer
Chordoma processed this record on December 01, 2015