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

January 21, 2015 updated by: University of California, San Francisco

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Decrease in Thyroglobulin Level
Time Frame: Baseline, 16 weeks
Number of participants with decreased thyroglobulin level after study treatment
Baseline, 16 weeks
Decrease in Tumor Size
Time Frame: Baseline, 16 weeks
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
Time Frame: Baseline, 10 weeks
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
Time Frame: 17 weeks
Number of participants experiencing > Grade 1 adverse events (including fatigue) attributable to study treatment
17 weeks
Survival
Time Frame: up to 10 years post-study treatment
up to 10 years post-study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

August 28, 2007

First Submitted That Met QC Criteria

September 4, 2007

First Posted (Estimate)

September 5, 2007

Study Record Updates

Last Update Posted (Estimate)

February 3, 2015

Last Update Submitted That Met QC Criteria

January 21, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Valproic Acid

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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