Neoplasms

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Thyroid Neoplasms

Thyroid Diseases

Carcinoma

Carcinoma, Neuroendocrine

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nintedanib

Protein Kinase Inhibitors

Enzyme Inhibitors

Nintedanib should be administered orally at a dose of 200 mg twice daily.

Placebo should be administered orally at a dose of 200 mg twice daily. Cross-over to nintedanib is allowed after progression.

Placebo

Martin Schlumberger, MD

For the treatment of thyroid cancer with the so called targeted therapy the angiogenesis pathway has several potential targets. The Receptors for Vascular endothelial growth factor (VEGF) and especially VEGFR-2 is considered to be crucial for the initiation of the formation as well as the maintenance of tumor vasculature.

In thyroid cancer these VEGF receptors (VEGFR-1, VEGFR-2), VEGF itself and receptors of the fibroblast growth factor (FGF) and for the platelet-derived growth factor (PDGF) are often overexpressed. Other cells as pericytes and smooth muscle cells that are also involved in tumor angiogenesis express these receptors as well.

Inhibitors of the VEGFR or PDGFR pathway have been tested in thyroid cancer with positive results. However there is no treatment that is generally considered as standard of care for patients with differentiated thyroid cancer (DTC) or medullar thyroid cancer (MTC) who have progressed on one line of therapy. The classical cytotoxic chemotherapy has not shown a clinically meaningful benefit yet.

Nintedanib is a triple angiogenesis inhibitor which inhibits receptors of VEGF, FGF and PDGF. Therefore it might act not only on endothelial cells but also on pericytes and smooth muscle cells. Nintedanib also interacts with other kinases such as RET. Because of this multi-kinase activity rationale exists to investigate the effect in MTC and DTC.

Because it targets these three major angiogenesis signaling pathways it might prevent further tumor growth and related tumor escape mechanisms. Therefore nintedanib may be active in patients who have progressed on agents that target only one pathway.

Nintedanib(BIBF1120) in Thyroid Cancer

A Phase II Study Exploring the Safety and Efficacy of Nintedanib (BIBF1120) as Second Line Therapy for Patients With Either Differentiated or Medullary Thyroid Cancer Progressing After First Line Therapy.

This study will use RECIST 1.1 to measure PFS

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

This study will use RECIST 1.1 to measure RR

This study will use RECIST 1.1 to measure duration of response

The biomarker study in this protocol is exploratory in nature.Spearman Correlation Coefficient will be computed to quantify the relationship between biomarkers and between biomarkers and clinical parameters (e.g. age). Fisher's exact test or Wilcoxon rank sum test will be used to assess the significance of these relationships.

European Organisation for Research and Treatment of Cancer - EORTC

Symptoms and General Pathology

Recurrence

Bone Density Conservation Agents

Vasodilator Agents

Amino Acids

Other Dietary Supplements

Vaccines

Calcitonin

Salmon calcitonin

Calcitonin Gene-Related Peptide

Katacalcin

N-Methylaspartate

Aspartic Acid

Brewer's Yeast

Asparagine

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

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.

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

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.

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.

QUILT-3.006 for Recurrent Medullary Thyroid Cancer

A Phase 2 Study of GI-6207 in Patients With Recurrent Medullary Thyroid Cancer

National Cancer Institute (NCI)

NantCell, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nintedanib(BIBF1120) in Thyroid Cancer	NCT01788982	Medullary Thyro... Differentiated ...	Nintedanib Placebo	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
QUILT-3.006 for Recurrent Medullary Thyroid Cancer	NCT01856920	Medullary Thyro...	GI-6207 [Recomb...	18 Years - 100 Years	NantCell, Inc.

Spots Global Cancer Trial Database for medullary thyroid cancer (mtc)