Gland and Hormone Related Diseases

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Thyroid Neoplasms

Thyroid Carcinoma, Anaplastic

Carcinoma

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Endocrine Gland Neoplasms

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anaplastic Thyroid Cancer

60 mg (2 capsules of 30 mg capsules) will be given orally once a day 5 days on and 2 days off.

CUDC-907

Naris Nilubol, M.D.

Background:

The thyroid is a gland at the base of the throat. Thyroid cancer is a disease that people get when abnormal cells begin to grow in this gland. Researchers believe a new drug called CUDC-907 may be able to help people with thyroid cancer that has spread or has gotten worse.

Objective:

To see if CUDC-907 will shrink tumors in people with advanced thyroid cancer.

Eligibility:

People at least 18 years old who have been diagnosed with locally advanced and metastatic thyroid cancer.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Electrocardiogram (ECG) heart test.

Review of their symptoms and how they perform normal activities

A scan will be performed. Some will have a computed tomographic scan (CT) that takes pictures of the body using a small amount of radiation. Some will have magnetic resonance imaging (MRI) that uses a magnetic field to take pictures.

Bone scan (some participants)

Fludeoxyglucose (FDG) positron emission tomography (PET) scan to produce a tumor image.

A sample of their tumor from a previous surgery. They may have a biopsy of their tumor if a tumor sample is not available from a previous surgery.

Participants will be given CUDC-907 in tablet form. They will take it by mouth once a day for 5 days, then take 2 days off, each week.

While taking the study drug, participants will have study visits that repeat the screening tests.

After they stop treatment, participants will have 3 follow-up visits over a year. They will repeat some tests. Then participants will be contacted by phone or e-mail every 6 months....

Background:

* There are no standard or effective systemic therapies for metastatic or locally advanced poorly differentiated and undifferentiated thyroid cancer.
* Poorly differentiated and undifferentiated thyroid cancer are aggressive, with high mortality.
* CUDC-907 is a first-in-class dual inhibitor of histone deacetylase (HDAC) and PI3K signaling.
* Approximately 80% of poorly differentiated and undifferentiated thyroid cancers have driver mutations in the PI3K/AKT pathway or activation of the pathway.
* HDAC2 is upregulated in poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer, and CUDC-907 treatment reduces HDAC2 levels in thyroid cancer cells.
* CUDC-907 inhibits thyroid cancer cell growth, invasion and migration in vitro.
* In addition to inhibiting the PI3K/AKT signaling pathway, CUDC-907 inhibits the EGFR/RAS/RAF/MEK/ERK signaling pathway, which is also activated in poorly differentiated and undifferentiated thyroid cancer.
* CUDC-907 inhibits growth and metastases in a mouse model of metastatic thyroid cancer.
* We hypothesize that CUDC-907 will cause cancer regression in patients with metastatic and locally advanced poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer.

Objective:

-To determine response to CUDC-907 treatment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with locally advanced and metastatic poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer.

Eligibility:

* Age greater than or equal to 18 years
* Thyroid cancer that is refractory to or relapsed after standard treatment.
* Aggressive thyroid cancer confirmed on histology or cytologic analysis.
* Measurable disease.
* Last dose of chemotherapy or last radiotherapy treatment more than 4 weeks prior to starting treatment with this protocol, except for subjects with anaplastic/undifferentiated thyroid cancer who may enroll immediately after discontinuation of previous therapy.

Design:

* Open label, phase II trial to determine response to CUDC-907 treatment.
* Patients will be given 60 mg of CUDC-907 orally for 5 consecutive days followed by 2 days off (5/2 schedule).
* One cycle is 21 days. Patients may continue on treatment if there is no disease progression.
* Initial anatomic and functional imaging will be performed at enrollment and after 2 cycles of treatment. Thereafter, anatomic imaging will be performed every two cycles of treatment.

This is a single group assignment. All patients regardless of subtype of thyroid cancer received one single treatment and follow up plan with option to continue the treatment when scan was negative.

CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer

A Phase II Trial of CUDC-907 in Patients With Metastatic and Locally Advanced Thyroid Cancer

Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Time in days from initiation of treatment until tumor grows more than 20%. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.

Time in days from the initiation of treatment until death estimated by the Kaplan-Meier method.

The amount of time subject survives without disease progression is compared by patient tumor mutation status.

The amount of time subject survives without disease progression is compared by the protein levels of PI3K/AKT and epidermal growth factor receptor (EGFR)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/methyl ethyl ketone (MEK)/extracellular-signal regulated kinase (ERK) in tumor tissue.

The amount of time subject survives without disease progression is compared by the protein levels of HDAC2 and surviving in tumor tissue. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

National Cancer Institute (NCI)

Principal Investigator

CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.

CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.

CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.

Poorly Differentiated/Variants of Thyroid Cancer

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Mexican, Puerto Rican, Cuban, Central/So American

Not meeting definition for Hispanic or Latino

Race/Ethnicity, Customized

United States

Region of Enrollment

Dr. Naris Nilubol

Complete Response

Partial Response

Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

One participant was non-evaluable (withdrew consent).

Median Amount of Time Subject Survives Without Disease Progression After Treatment

CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.

CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.

CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.

All Participants

Participants are grouped together because of a small sample size and not enough power to compare the difference between two groups. No statistical analysis to be done.

Median Amount of Time Subject Survives After Therapy

This outcome measure was not done. Data was collected but the correlation between mutation status of tumor and progression-free survival was not performed because of only BRAF V600E and the loss of tumor protein 53 (TP53) heterozygosity were found on a single patient each. Since only 1 mutant was found for each, no analysis was done.

Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment

This outcome measure was not done. Data was collected but no samples were analyzed because the experiment was not technically successful due to inconclusive results from immunohistochemistry (study of protein levels in tumor tissue) analysis of P13K/AKT and EGFR/RAS/RAF/MEK/ERK proteins.

Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment

Anaplastic Cancer

This outcome measure was not done. Data was collected but not analyzed because the assessment of HDAC2 and survivin proteins cannot be reliably performed with consistent results.

Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment

Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

CUDC-907 for anaplastic thyroid cancer

CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer	NCT03002623	Thyroid Neoplas... Poorly Differen... Differentiated ...	CUDC-907	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer	NCT03002623	Thyroid Neoplas... Poorly Differen... Differentiated ...	CUDC-907	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer	NCT03002623	Thyroid Neoplas... Poorly Differen... Differentiated ...	CUDC-907	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)

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Spots Global Cancer Trial Database for hdac2

Every month we try and update this database with for hdac2 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hdac2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.