Valproic Acid (Depakote ER) in Patients With Advanced Thyroid Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs such as valproic acid may make thyroid cancers more radioiodine sensitive, which will allow for detection of tumor and make further ablation treatment effective.

Detailed Description
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PURPOSE: This phase II trial is studying how well valproic acid works in treating patients with thyroid cancers that do not respond well to other treatments.

Official Title
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A Phase II Trial of Valproic Acid (Depakote ER ®) in Patients With Advanced Thyroid Cancers of Follicular Origin, Who Are Thyroglobulin Positive/RAI Unresponsive

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Valproic Acid


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: DISEASE CHARACTERISTICS Diagnosis of advanced/poorly differentiated thyroid cancer of follicular cell origin that is radioiodine-unresponsive Cumulative dose of radioiodine < 800 mCi No radioiodine uptake on whole body scan within 18 months of enrollment Inoperable extensive locoregional tumor mass and/or metastatic spread Failed conventional therapy that included total thyroidectomy AND radioactive iodine I 131 ablation Elevated thyroglobulin level (>2ng/ml on thyroid hormone, >10ng/ml off thyroid hormone)or Tg-antibody positive PATIENT CHARACTERISTICS -18 years or older Entry lab results: Hemoglobin > 8.0 gm/dl Absolute Neutrophil Count > 750 cells/mm3 Platelet count > 75000/mm3 BUN < 1.5 times upper limit of normal (ULN) Creatinine < 1.5 times ULN Total protein > 6.4 Total bilirubin should be < 1.5 times ULN. AST (SGOT), ALT (SGPT), ALKP and amylase < 1.5 times ULN Amylase < 1.5 times ULN Albumin > 2.5 Ammonia < 1.5 times ULN EXCLUSION CRITERIA: Not pregnant No nursing within the past 3 months No allergy to valproic acid No coexisting malignancy other than basal cell carcinoma No hepatic disease or significant dysfunction Karnofsky score > 80 No pancreatitis No kidney dysfunction Fertile patients must use effective contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>If a patient exhibits increased radioiodine uptake on the Thyrogen scan post valproic acid therapy, patients will then prepare for ablative treatment and will remain on valproic acid for a total of 16 weeks, until receiving RAI ablation. | Drug: Valproic Acid<br>* OUTLINE: This is a pilot study. Patients receive valproic acid daily for 16 weeks. Dose increases on Days 4 and 8; dose remains the same for weeks 2-10. All patients will undergo a Thyrogen® (thyrotropin alfa for injection) RAI scan at entry to the study and after completion of 10 weeks of valproic acid treatment. Quality of life is assessed at the end of every week through a study diary. Patients are followed at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 17 (Schedule 1) weeks. Patients return for follow-up at 3, 6, and 12 months.<br>|
| Other: 2<br>If no increased uptake is seen, patients will continue on valproic acid for 6 additional weeks at an increased dosage, totaling an overall treatment time of 16 weeks as well. | Drug: Valproic Acid<br>* OUTLINE: This is a pilot study. Patients receive valproic acid daily for 16 weeks. Dose increases on Days 4 and 8; dose remains the same for weeks 2-10. All patients will undergo a Thyrogen® (thyrotropin alfa for injection) RAI scan at entry to the study and after completion of 10 weeks of valproic acid treatment. Quality of life is assessed at the end of every week through a study diary. Patients are followed at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 17 (Schedule 1) weeks. Patients return for follow-up at 3, 6, and 12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in Thyroglobulin Level | Number of participants with decreased thyroglobulin level after study treatment | Baseline, 16 weeks | 
| Decrease in Tumor Size | Number of participants with decreased tumor size after study treatment | Baseline, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased Radioactive Iodine Uptake | Number of participants with increased radioiodine uptake on the Thyrogen scan post valproic acid therapy | Baseline, 10 weeks | 
| Side Effects of Drugs Affecting Quality of Life | Number of participants experiencing > Grade 1 adverse events (including fatigue) attributable to study treatment | 17 weeks | 
| Survival |  | up to 10 years post-study treatment |