Valproic Acid (Depakote ER) in Patients With Advanced Thyroid Cancer - Full Text View

Sponsors and Collaborators:	University of California, San Francisco National Cancer Institute (NCI)
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00525135

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 II

MedlinePlus related topics: Cancer Head and Neck Cancer Thyroid Cancer

Drug Information available for: Divalproex sodium Valproate Sodium Valproic acid Thyroid Thyroglobulin Thyrotropin alfa Thyrotropin

U.S. FDA Resources

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

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 ]

Estimated Enrollment:	25
Study Start Date:	August 2007
Estimated Study Completion Date:	August 2009
Estimated Primary Completion Date:	August 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.

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

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

Contacts

Contact: Ileana Sansano, MPH

415-353-9970

sansanoi@surgery.ucsf.edu

Locations

United States, California
UCSF Comprehensive Cancer Center	Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office UCSF Comprehensive Cancer Center 877-827-3222

Sponsors and Collaborators

University of California, San Francisco

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Electron Kebebew, MD

University of California, San Francisco

More Information

Responsible Party:	University of California, San Francisco ( Electron Kebebew, MD )
Study ID Numbers:	Valproic Acid
Study First Received:	August 28, 2007
Last Updated:	May 5, 2008
ClinicalTrials.gov Identifier:	NCT00525135
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Study placed in the following topic categories:

Thyroid Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Endocrinopathy

Valproic Acid
Thyroid Diseases
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 14, 2009