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

Inclusion Criteria

- INCLUSION CRITERIA:

1. 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.

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

3. 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.).

4. 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%).

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

6. 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.

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

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

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

10. Life expectancy of greater than three months.

11. 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.

12. 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:

1. Allergy to valproic acid.

2. Current coexisting malignancy other than basal cell carcinoma.

3. 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.

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

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

6. Seizure disorder.