QUILT-3.006 for Recurrent Medullary Thyroid Cancer

NCT01856920 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: QUILT-3.00613-C-0095
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- GI-6207 is an experimental cancer vaccine made with baker's yeast. The yeast has been modified to help the immune system target a protein called CEA. CEA is found on the surface of some kinds of tumor cells, including thyroid cancer cells. Researchers want to see if GI-6207 can encourage the body's immune system to attack and kill tumor cells that contain the CEA protein. They will test to see whether this vaccine is a safe and effective treatment for medullary thyroid cancer that has not responded to earlier treatments. Objectives: \- To test the safety and effectiveness of the GI-6207 vaccine for advanced medullary thyroid cancer. Eligibility: \- Individuals at least 18 years of age who have medullary thyroid cancer that has not responded to earlier treatments. Design:

• Participants will be screened with a physical exam and medical history. They will provide blood and tumor samples and have an imaging study of the neck and chest. They will also have a skin test to make sure that they are not allergic to the yeast in the vaccine.
• Participants will be divided into two groups. One group will start to take GI-6207 immediately for 1 year. The second group will have 6 months of monitoring and tests with no vaccine, and then will take GI-6207 for 1 year.
• GI-6207 will be given every other week for the first seven visits (about 3 months), and then monthly for the remaining year of treatment. It will be given as injections beneath the arm and in the upper thigh. These locations will help the vaccine enter the lymph nodes and reach the immune system more quickly.
• Participants will be monitored with frequent blood and urine tests and imaging studies.
• Participants will have regular follow-up visits after their year of study vaccines.

Conditions

Medullary Thyroid Cancer (MTC)

Keywords

Calcitonin; T-cells; Immune Response; HLA Patients; Vaccine

Outcome Measures

Primary Outcomes (1)

• Calcitonin Growth Rate

  NCI developed an equation based on the assumption that the change of a tumor's quantity during therapy results from 2 independent component processes: an exponential (first-order kinetics) decrease/regression and an exponential regrowth of the tumor. The equation is f(t) = exp(-d\*t)+exp(g\*t) (A) where exp is the base of the natural logarithm, and f(t) is the MTC calcitonin measurement at time t in days, divided by the tumor measurement at day 0, the time at which treatment is commenced. Rate decay constant d (days\^(-1) )represents the exponential decrease of the tumor marker signal during therapy. Rate growth constant g (days-\^(1) )represents the exponential growth of the tumor during treatment. For each patient an attempt to fit Equation (A) to each data set for which more than one data point is available. Linear regressions to evaluate the relationship between the growth rate constant,g, or other parameters will be implemented using the polynomial linear routine of Sigmaplot 9.0.

  after 6 months of therapy

Study Arms (2)

A

EXPERIMENTAL

GI-6207 for 1 year

Biological: GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)]

B

EXPERIMENTAL

6 months of surveillance followed by GI-6207 for 1 year

Biological: GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)]

Interventions

GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)] BIOLOGICAL

GI-6207 is a heat-killed, recombinant yeast-based vaccine engineered to express the full length human carcinoembryonic antigen (CEA), with a modified gene coding sequence to code for a single amino acid substitution (asparagine to aspartic acid) at the native protein amino acid position 610, which is designed to enhance immunogenicity. A plasmid vector containing the modified human CEA gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wild-type yeast) to produce the final recombinant vaccine product.

A; B

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria for participation:
• Diagnosis: Patients must have histologically confirmed medullary thyroid cancer by the Laboratory of Pathology or a pathology report and history consistent with medullary thyroid cancer. It is not uncommon for a secondary, minor pathologic focus of another form of thyroid cancer to be coincidentally found in 15-20% of patients with medullary thyroid cancer. In such cases, eligibility is based on the discretion of the investigator.
• Patients must have evidence of metastatic medullary thyroid cancer including disease that is evaluable on bone, CT scan or MRI. (Patients who are surgical candidates and potentially rendered disease free with surgical resection are not eligible.)
• Patients must have elevated calcitonin levels, greater than 8 pg/mL in females and 16 pg/mL in males
• Patients with minimal or no disease related-symptoms (Minimal symptoms will include those that do not affect activities of daily living or pain that does not require regularly scheduled narcotics.)
• No brain metastasis, history of seizures, encephalitis, or multiple sclerosis.
• Age greater than or equal to 18 years
• ECOG performance status of 0-1 at study entry (Karnofsky greater than or equal to 70)
• No systemic steroid use within 2 weeks prior to initiation of experimental therapy. Limited doses of systemic steroids to prevent IV contrast, allergic reaction or anaphylaxis (in patients who have known contrast allergies) are allowed.
• Hematological eligibility parameters
• Granulocyte count greater than or equal to 1,500/mm\^3
• Platelet count greater than or equal to 100,000/mm\^3
• Hemoglobin greater than or equal to 9 g/dL
• Biochemical eligibility parameters (within 16 days of starting therapy)
• Baseline renal function:

You may not qualify if:

• Patients with any of the following will not be eligible for participation in this study:
• 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 recent history of autoimmune disease requiring therapy, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis. This requirement is due to the potential risks of exacerbating autoimmunity. However, patients with vitiligo may be enrolled. (Patients with history of autoimmune thyroid conditions will be allowed as these patients will be on replacement medications.)
• Concurrent use of systemic steroids, except for physiologic doses of systemic steroid replacement or local (topical, nasal, eye drops 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.
• Pregnant or breast-feeding women, due to the unknown effects of GI-6207 on the fetus or infant.
• Serious inter-current medical illness which would interfere with the ability of the patient to carry out the treatment program.
• Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.
• Patients with pericardial masses \>1 cm or thoracic lesions larger than 2 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.
• Participation in another interventional clinical trial at the time of enrollment.
• 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 with second malignancy within 3 years of enrollment; patients treated surgically with a curative intent, such as non-melanoma skin cancers, localized kidney cancer or carcinoma in situ of the bladder, are not excluded. Patients with MEN2 and a history of pheochromocytoma will also not be excluded. In addition patients with prostate cancer who do not require systemic therapy will not be excluded. (A secondary, minor pathologic focus of another form of thyroid cancer may be coincidentally found in 15-20% of patients with medullary thyroid cancer. In such cases, eligibility is based on the discretion of the investigator.

Sponsors & Collaborators

• NantCell, Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

NIH Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Peshwa MV, Shi JD, Ruegg C, Laus R, van Schooten WC. Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide. Prostate. 1998 Jul 1;36(2):129-38. doi: 10.1002/(sici)1097-0045(19980701)36:23.0.co;2-d.

  PMID: 9655265 BACKGROUND

• Fong L, Small EJ. Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol. 2008 Nov 10;26(32):5275-83. doi: 10.1200/JCO.2008.17.8954. Epub 2008 Oct 6.

  PMID: 18838703 BACKGROUND

• O'Day SJ, Hamid O, Urba WJ. Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer. 2007 Dec 15;110(12):2614-27. doi: 10.1002/cncr.23086.

  PMID: 18000991 BACKGROUND

• Del Rivero J, Donahue RN, Marte JL, Gramza A, Bilusic M, Cordes L, Karzai F, Schlom J, Gulley JL, Madan RA. A phase 2 study of GI-6207 in patients with recurrent medullary thyroid cancer. Oncologist. 2025 Dec 30:oyaf429. doi: 10.1093/oncolo/oyaf429. Online ahead of print.

  PMID: 41467761 DERIVED

• Del Rivero J, Donahue RN, Marte JL, Gramza AW, Bilusic M, Rauckhorst M, Cordes L, Merino MJ, Dahut WL, Schlom J, Gulley JL, Madan RA. A Case Report of Sequential Use of a Yeast-CEA Therapeutic Cancer Vaccine and Anti-PD-L1 Inhibitor in Metastatic Medullary Thyroid Cancer. Front Endocrinol (Lausanne). 2020 Aug 7;11:490. doi: 10.3389/fendo.2020.00490. eCollection 2020.

  PMID: 32849281 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Medullary

Interventions

yeast-CEA vaccine

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Office
• Organization: ImmunityBio

Bobby.Reddy@immunitybio.com

855-797-9277

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 20, 2013
• Study Start: March 26, 2013
• Primary Completion: May 8, 2018
• Study Completion: May 8, 2018
• Last Updated: July 9, 2024
• Results First Posted: July 9, 2024

Record last verified: 2024-06

Locations

US (1)