QUILT-3.011 Phase 2 Yeast-Brachyury Vaccine Chordoma

A Randomized, Double-Blind, Phase 2 Trial of GI-6301 (Yeast-Brachyury Vaccine) Versus Placebo in Combination With Standard of Care Definitive Radiotherapy in Locally Advanced, Unresectable, Chordoma

This is a phase 2 clinical trial to determine whether the yeast-brachyury vaccine GI-6301 improves the effectiveness of radiation for patients with localized chordoma. Chordoma patients with inoperable or residual tumor who do not have metastases and are planning to be treated with definitive (>70Gy) radiation were enrolled. Patients were randomized to receive radiation plus the vaccine or radiation plus a blinded placebo. The study compared the outcomes of patients treated with radiation with and without the vaccine to determine whether the vaccine can increase the chances of shrinking the tumor and/or preventing further tumor growth.

Study Overview

• Status: Completed
• Conditions: Chordoma
• Intervention / Treatment: Biological: GI-6301 Vaccine (Yeast- Brachyury); Radiation: Radiotherapy; Device: wGT3X-BT Actigraph; Other: Placebo

Detailed Description

Chordoma is a rare disease, affecting about 3,000 people in the United States. There have been indications of clinical benefit in patients with chordoma enrolled on the phase I trial of GI-6301.

PRIMARY OBJECTIVE: To determine if there is a difference in overall response rate (ORR) defined as complete response (CR) or partial response (PR) by RECIST 1.1 after up to 24 months among patients with Chordoma who are treated with radiation plus placebo vs. radiation plus vaccine.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • NIH Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

Participants must meet the following criteria for participation:

1. Diagnosis: Patients must have histologically confirmed chordoma by the Laboratory of Pathology, NCI, which is localized (no evidence of metastatic disease), unresectable and they must have planned radiation therapy, to at least one targeted lesion with evidence of growth prior to enrollment. The tentative radiation plan at enrollment must be in compliance with the required radiation doses. This can be given in standard or hypofractionated dosing with any technique deemed most appropriate by the treating radiation oncologist if other requirements are not met.
2. Patients must have disease that is measurable by RECIST version 1.1.
3. Fresh or archived tumor specimen must be available for correlative studies.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at study entry (Karnofsky greater than or equal to 70)
5. Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of GI-6301 (Yeast Brachyury vaccine) in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
6. Prior Therapy: Patients must have fully recovered from prior surgery before enrollment. Prior radiation therapy is allowed provided the radiation field can safely irridated in the opinion of the treating radiation oncologist.

7. Patients must have normal organ and marrow function as defined below:

   • Serum creatinine less than or equal to 1.5 X upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.
   • ALT and AST less than or equal to 3 X the upper limits of normal.
   • Total bilirubin less than or equal to 1.5 X upper limit of normal OR in patients with Gilbert s syndrome, a total bilirubin less than or equal to 3.0.
   • Hematological eligibility parameters (within16 days of starting therapy):

   Granulocyte count greater than or equal to 1,500/mm3

   Platelet count greater than or equal to 100,000/mm3

8. 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.
9. Patients must not have a history of yeast allergy. If patient has a questionable history of allergy to yeast, a yeast skin test can be performed. Patients would be eligible if skin test is negative.
10. 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:

1. 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 thyroiditis on appropriate replacement therapy may be enrolled.
• 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.
• Chronic hepatitis infection, including B and C, because potential immune impairment caused by these disorders may diminish the effectiveness of this immunologic therapy.
• 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.
• Patients may not be on systemic steroids within 4 weeks of enrolling on study with the exception of physiologic replacement doses (for instance in the case of adrenal insufficiency) or steroid premedication for baseline MRI and/or CT in the case of subjects with known contrast dye allergies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GI-6301 Vaccine; Radiation + GI-6301 Vaccine + Actigraph	Biological: GI-6301 Vaccine (Yeast- Brachyury); GI-6301 Vaccine 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.; Radiation: Radiotherapy; Standard of care; Device: wGT3X-BT Actigraph; wGT3X-BT is small, non-invasive, portable watch accelerometer worn on the subject's wrist for Cycle 1 through Cycle 9
Placebo Comparator: Placebo; Radiation + Placebo + Actigraph	Radiation: Radiotherapy; Standard of care; Device: wGT3X-BT Actigraph; wGT3X-BT is small, non-invasive, portable watch accelerometer worn on the subject's wrist for Cycle 1 through Cycle 9; Other: Placebo; Placebo will consist of USP-grade or equivalent 0.9% Sodium Chloride for Injection. Doses of placebo will be drawn into labeled syringes by an independent, unblinded pharmacist or designee.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Difference in overall response rate among patients with Chordoma who are treated with radiation plus placebo vs. radiation plus vaccine. Overall response rate (ORR) defined as complete response (CR) or partial response (PR) by RECIST 1.1 in the irradiated tumor site after up to 24 months among patients with Chordoma who are treated with radiation plus vaccine vs. radiation plus placebo Complete response (CR; disappearance of all target lesions and no new lesions) or partial response (PR; >=30% decrease in the sum of the greatest diameter).	Up to 24 months

Collaborators and Investigators

• Sponsor: NantCell, Inc.
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Wedekind MF, Widemann BC, Cote G. Chordoma: Current status, problems, and future directions. Curr Probl Cancer. 2021 Aug;45(4):100771. doi: 10.1016/j.currproblcancer.2021.100771. Epub 2021 Jul 1.

Helpful Links

• NIH Clinical Center Detailed Web Page
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: March 4, 2015
• First Submitted That Met QC Criteria: March 6, 2015
• First Posted (Estimated): March 9, 2015

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Overall Response Rate; Tumor Infiltrating Lymphocytes; Immune Activation; Cross-Over; T Cell Response
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Chordoma
• Other Study ID Numbers: QUILT-3.011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No