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Protocol Details

A Phase II Trial of Valproic Acid in Patients with Advanced Thyroid Cancers of Follicular Origin

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

10-C-0041

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 120

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Depakote;
Poorly Differentiated Thyroid Cancer;
RAI Uptake;
Thyrogen

Recruitment Keyword(s)

None

Condition(s)

Thyroid Neoplasm

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Valproic Acid

Supporting Site

National Cancer Institute

Background:

- Patients who have advanced thyroid cancer have a low long-term survival rate. These types of thyroid cancer do not respond well to conventional surgery or radiation, or to specific thyroid cancer treatments such as radioactive iodine treatment and thyroid hormone for thyroid stimulating hormone (TSH) suppression.

- Valproic acid has long been approved as an anticonvulsant to treat seizures in patients with epilepsy. It has also been used to treat bipolar disorder. Recent studies have shown that valproic acid has promising effects in thyroid cancer treatment because it may help destroy cancer cells and help conventional treatments be more effective. However, valproic acid is not approved for thyroid cancer and is therefore an investigational drug.

Objectives:

- To determine whether valproic acid can inhibit tumor growth or induce tumor cell death.

- To determine whether valproic acid can make tumor cells increase their uptake of radioiodine.

Eligibility:

- Individuals at least 18 years of age who have advanced-stage thyroid cancer that is either unresponsive to conventional treatments or fails to absorb radioiodine.

Design:

- Eligible participants will continue on the standard thyroid hormone suppression therapy and begin receiving valproic acid for a total of 10 weeks. Participants will keep a study diary to record doses and side effects, and will have regular clinic visits to provide blood samples and receive additional valproic acid.

- After 10 weeks, participants will have a Thyrogen scan to measure radioiodine uptake after valproic acid therapy. Tumor biopsies and blood samples will be taken at this time.

- If there is increased radioiodine uptake on the scan, participants will have additional radioiodine therapy.

-If there is no increased uptake on the scan, participants will continue on valproic acid for 7 more weeks. After 16 total weeks of treatment, additional blood samples and scans will be taken. Participants may continue to take valproic acid if the thyroid cancer appears to be responding to the treatment.

- Follow-up visits will be scheduled at 3, 6, 9 (for patients continuing on valproic acid only), and 12 months.

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Eligibility

INCLUSION CRITERIA:

a. Advanced/poorly differentiated thyroid cancers of follicular cell origin that have no uptake (less than 1%) on radioiodine scan or are unresponsive to radioiodine therapy. Unresponsiveness to radioiodine therapy is defined as a patient s thyroglobulin not falling to less than 2ng/ml within 6 months after previous radioiodine ablative treatment.

b. Extensive (invasive) loco-regional tumor mass and/or metastatic spread, rendering patient inoperable.

c. Thyroglobulin (Tg) levels greater than or equal to 100 ng/ml in the absence of Tg antibodies. Patients who are Tg-antibody (Tg-Ab) positive may be included despite a lower Tg level if they have detectable disease on cross sectional imaging. (The presence of Tg-Ab may lead to falsely low Tg levels and therefore render the Tg a less sensitive marker of disease. However, Tg-Ab has been shown to also act as a tumor marker, and will be used as an endpoint for the study in patients who are Tg-Ab positive.).

d. Within 18 months of enrollment, patients must have had an RAI scan, showing no or therapeutically insignificant RAI uptake (less than or equal to 1%).

e. Initial therapy must have included total/near-total thyroidectomy and RAI ablation therapy.

f. Patients must have had no chemotherapy, radiotherapy, or biologic therapy for their malignancy in the month prior to treatment and must have recovered from all side effects of therapeutic and diagnostic interventions.

g. Greater than or equal to 18 years of age.

h. Must be able to understand and sign the Informed Consent Document.

i. Clinical performance status of ECOG less than or equal to 1.

j. Life expectancy of greater than three months.

k. Women of childbearing potential must have a negative serum beta-HCG within 72 hours prior to study entry and must be willing to practice effective birth control to prevent pregnancy while receiving treatment and for three months after treatment is discontinued. All males of child fathering potential must also be willing to practice effective birth control.

l. Laboratory results must be within the following parameters before entry:

-Absolute Neutrophil Count greater than 750 cells/mm(3)

-Hemoglobin greater than 8.0 gm/dl

-Platelet count greater than 75000/mm(3)

-Creatinine less tha 1.5 times ULN

-Total protein greater than 6.4.

-Total bilirubin should be less than 1.5 times ULN.

-AST (SGOT), ALT (SGPT) less than 1.5 times ULN.

-Amylase less than 1.5 times ULN

-Ammonia less than 1.5 times ULN

EXCLUSION CRITERIA:

a. Allergy to valproic acid.

b. Current coexisting malignancy other than basal cell carcinoma.

c. Women of child-bearing potential who are pregnant or breastfeeding.

Valproic acid is a known teratogen, causing primary neural tube defects, facial abnormalities, and skeletal malformation; therefore pregnant women will be excluded. Additionally, patients that become pregnant while on study protocol will be discontinued immediately.

d. Active systemic infections, coagulation disorders or other major medical illnesses.

e. Patients taking tolbutamide, warfarin, zidovudine, benzodiazapines, clonazepam, diazepam.

f. Seizure disorder.


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Citations:

Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006 May 10;29 (18):2164- 7.

Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995]. Cancer. 1998 Dec 15;83(12):2638-48.

Goretzki PE, Simon D, Frilling A, Witte J, Reiners C, Grussendorf M, Horster FA, R(SqrRoot)(Delta)her HD. Surgical reintervention for differentiated thyroid cancer. Br J Surg. 1993 Aug;80(8):1009-12.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Electron Kebebew, M.D.
National Cancer Institute (NCI)
BG 10-CRC RM 4-5952
10 CENTER DR
BETHESDA MD 20814
(301) 496-5049
kebebewe@mail.nih.gov

Candice M. Cottle-Delisle, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4-3152
10 Center Drive
Bethesda, Maryland 20892
(301) 402-4395
cottlec@mail.nih.gov

Erinn Hopkins
National Institutes of Health
Building 10
Room 3-5581
10 Center Drive
Bethesda, Maryland 20892
(301) 496-6457
hopkinsem@mail.nih.gov

Clinical Trials Number:

NCT01182285

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