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

This study has been terminated.
(PI left university and study was halted prematurely. No data was analyzed.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00525135
First received: August 28, 2007
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: Valproic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Decrease in thyroglobulin level and tumor size [ Time Frame: 16 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radioactive iodine uptake [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Side effects of drugs, quality of life and survival [ Time Frame: 17 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: August 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00525135

Locations
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Electron Kebebew, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00525135     History of Changes
Other Study ID Numbers: Valproic Acid
Study First Received: August 28, 2007
Last Updated: April 2, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Thyroid Neoplasms
Head and Neck Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Endocrine System Diseases
Thyroid Diseases
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 29, 2014