A Phase II Trial of Valproic Acid in Patients With Advanced Thyroid Cancers of Follicular Origin
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
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
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine if valproic acid will inhibit thyroid cancer growth, as evidenced by a decrease in thyroglobulin level, and tumor size.
Electron Kebebew, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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