QUILT-3.006 for Recurrent Medullary Thyroid Cancer

Phase 2

Completed

Conditions: Medullary Thyroid Cancer (MTC)

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

Registration Number: NCT01856920

Lead Sponsor: NantCell, Inc.

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.

Detailed Description: BACKGROUND:

* CEA is overexpressed in multiple malignancies, including medullary thyroid cancer where CEA is universally expressed on tumor cells.

* There is no standard treatment for patients with asymptomatic or minimally symptomatic, metastatic medullary thyroid cancer. The only effective FDA-approved therapy (vandetanib) comes with significant toxicity, so it is not used until patients have symptomatic or rapidly progressing disease.

* Preclinical studies have shown that GI-6207 can induce a strong immune response to CEA as well as therapeutic anti-tumor responses.

* A previous Phase I GI-6207 study has demonstrated safety and enhanced immune response in some patients.

* Preliminary data suggests that tumor growth rates can be calculated in medullary thyroid cancer patients within 3 months

* Retrospective data from prostate cancer studies suggest that vaccines can alter tumor growth rates within 3-4 months

OBJECTIVES:

Primary:

-To determine the effect of GI-6207 on calcitonin growth rate kinetics after 6 months of therapy in patients with medullary thyroid cancer

ELIGIBILITY:

* Patients will have evidence of metastatic medullary thyroid cancer including disease that is evaluable on bone or CT scan.

* 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 schedule narcotics.)

* ECOG 0-1

* No previous chemotherapy

* No previous vandetanib

* Should have no autoimmune diseases; no evidence of being immunocompromised; no serious inter-current medical illness; no cardiac disease; no prior splenectomy. (History of previous thyroid autoimmune disease will be allowed as these patients will have had total thyroidectomy.)

* No brain metastasis, history of seizures, encephalitis, or multiple sclerosis

* No pericardial-based masses greater than 1 cm or thoracic lesions larger than 2 cm

Design:

* Randomized, phase 2 study to determine the effect of GI-6207 on calcitonin growth rate after 6 months of GI-6207

* Patients will be randomized to either initial GI-6207 therapy or 6 months of surveillance followed by GI-6207 therapy.

* GI-6207 will be administered subcutaneously at 4 sites at dose of 10 yeast units per site, biweekly for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly up to 1 year of treatment. (For patients randomized to surveillance and then GI-6207, they will get a full year of GI-6207 after a 6 month surveillance period.)

* Once patients have completed one year of therapy with GI-6207, patients without radiographic progression will have the option to receive vaccine every 3 months for an additional 12 months. Patients who remain on vaccine will continue to be scanned every 3 months.

* Immune monitoring via apheresis will be done prior to enrollment and at 6 months for all appropriate and consenting patients. Patients who are evaluable for immunologic response by the ELISPOT Assay (HLA 02, 03 and 24) will have apheresis at start of GI-6207 therapy and then every 3 months while on GI-6207 treatment when feasible.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)]	6 months of surveillance followed by GI-6207 for 1 year
A	GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)]	GI-6207 for 1 year

Primary Outcome Measures

Name	Time	Method
Calcitonin Growth Rate	after 6 months of therapy	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.

Secondary Outcome Measures