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

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.

Study Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Valproic Acid
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Other: 1
  • 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.
• Other: 2
  • 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.

Primary Measures

• Decrease in thyroglobulin level and tumor size
  • Time Frame: 16 months
    Safety Issue?: No

Secondary Measures

• Radioactive iodine uptake
  • Time Frame: 10 weeks
    Safety Issue?: No
• Side effects of drugs, quality of life and survival
  • Time Frame: 17 weeks
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

Electron Kebebew, MD Principal Investigator University of California, San Francisco  

Overall Contact: Ileana Sansano, MPH 415-353-9970 sansanoi@surgery.ucsf.edu

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00525135

Study ID Number: Valproic Acid

ClinicalTrials.gov Identifier: NCT00525135

Health Authority: United States: Institutional Review Board