A Phase II Trial of Valproic Acid in Patients With Advanced Thyroid Cancers of Follicular Cell Origin
- Patients who have advanced thyroid cancer have a low long-term survival rate. These types of thyroid cancer do not respond well to conventional surgery or radiation, or to specific thyroid cancer treatments such as radioactive iodine treatment and thyroid hormone for thyroid stimulating hormone (TSH) suppression.
- Valproic acid has long been approved as an anticonvulsant to treat seizures in patients with epilepsy. It has also been used to treat bipolar disorder. Recent studies have shown that valproic acid has promising effects in thyroid cancer treatment because it may help destroy cancer cells and help conventional treatments be more effective. However, valproic acid is not approved for thyroid cancer and is therefore an investigational drug.
- To determine whether valproic acid can inhibit tumor growth or induce tumor cell death.
- To determine whether valproic acid can make tumor cells increase their uptake of radioiodine.
- Individuals at least 18 years of age who have advanced-stage thyroid cancer that is either unresponsive to conventional treatments or fails to absorb radioiodine.
- Eligible participants will continue on the standard thyroid hormone suppression therapy and begin receiving valproic acid for a total of 10 weeks. Participants will keep a study diary to record doses and side effects, and will have regular clinic visits to provide blood samples and receive additional valproic acid.
- After 10 weeks, participants will have a Thyrogen scan to measure radioiodine uptake after valproic acid therapy. Tumor biopsies and blood samples will be taken at this time.
- If there is increased radioiodine uptake on the scan, participants will have additional radioiodine therapy.
- If there is no increased uptake on the scan, participants will continue on valproic acid for 7 more weeks. After 16 total weeks of treatment, additional blood samples and scans will be taken. Participants may continue to take valproic acid if the thyroid cancer appears to be responding to the treatment.
- Follow-up visits will be scheduled at 3, 6, 9 (for patients continuing on valproic acid only), and 12 months.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Valproic Acid in Patients With Advanced Thyroid Cancers of Follicular Origin|
- To determine if valproic acid will inhibit thyroid cancer growth, as evidenced by a decrease in thyroglobulin level, and tumor size. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- To determine if valproic acid therapy will induce differentiation of and therefore increase uptake of radioactive iodine by the tumor cells. To determine the effect of valproic acid on differentiation markers. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
Increased radioiodine uptake/no increasedradioiodine uptake
Drug: Valproic Acid
Drug: Liothyronine Sodium
Patients who exhibit an increased radioiodine uptake on Thyrogen scan post valproic acid therapy at week 10. Begin Cytomel for 4 weeks (25 micrograms twice a day)
Patients who have advanced differentiated thyroid cancers (Stage IV) have a five-year survival of only 25%. Clinically this results in more aggressive growth, metastasis, decreased or loss of iodine uptake in the tumor, and tumors that may be refractory to conventional treatment: surgical resection, radioactive iodine treatment and thyroid hormone for Thyroid Stimulating Hormone (TSH) suppression.
In thyroid cancer, valproic acid, at clinically achievable concentrations, has an antiproliferative and differentiating effect.
We hypothesize that valproic acid may inhibit proliferation and induce differentiation in thyroid cancer cells so that 131-I may detect residual disease and be more effective for radioiodine ablation of thyroid cancer cells of follicular cell origin.
The primary goal of this study is to determine if valproic acid will have an antineoplastic and differentiation effect in patients with advanced and or metastatic thyroid cancer of follicular cell origin.
Unresectable advanced and/or poorly differentiated thyroid cancers of follicular cell origin (excluding anaplastic and medullary thyroid cancer) that have no uptake (less than 1%) on radioiodine scan or are unresponsive to radioiodine therapy.
Elevated serum thyroglobulin (Tg) level (greater than 100ng/ml on thyroid hormone; greater than 10ng/ml off thyroid hormone).
This will be an open label phase II study to assess the efficacy of valproic acid therapy as an antiproliferative and differentiation agent in patients with incurable differentiated thyroid cancer (unresponsive and/or radioiodine negative and unresectable).
Oral valproic acid will be administered to reach a therapeutic serum level (50 to 100 microgram/ml).
The number of patients to be enrolled is 25 with an interim analysis of response once 13 patients are evaluable for response. It is anticipated that five patients may be enrolled per year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01182285
|Contact: Candice M Cottle-Delisle, R.N.||(301) firstname.lastname@example.org|
|Contact: Electron Kebebew, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Kaitlyn Chambers 301-402-4395 firstname.lastname@example.org|
|Contact: Roxanne Merkel (301) 402-4395 email@example.com|
|Principal Investigator:||Electron Kebebew, M.D.||National Cancer Institute (NCI)|