Valproic Acid in Treating Patients with Advanced Thyroid Cancer of Follicular Origin
This phase II trial studies how well valproic acid works in treating patients with thyroid cancer of follicular origin that has spread to other places in the body and usually cannot be cured or controlled with treatment. Valproic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria
- Advanced/poorly differentiated thyroid cancers of follicular cell origin that have no uptake (< 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 2 ng/ml within 6 months after previous radioiodine ablative treatment
- Extensive (invasive) loco-regional tumor mass and/or metastatic spread, rendering patient inoperable
- 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)
- Within 18 months of enrollment, patients must have had a radioactive iodine (RAI) scan, showing no or therapeutically insignificant RAI uptake (=< 1%)
- Initial therapy must have included total/near-total thyroidectomy and RAI ablation therapy
- 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
- Must be able to understand and sign the informed consent document
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or equal to 1
- Life expectancy of greater than three months
- Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (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
- Absolute neutrophil count > 750 cells/mm^3
- Hemoglobin > 8.0 gm/dl
- Platelet count > 75000/mm^3
- Creatinine < 1.5 times upper limit of normal (ULN)
- Total protein > 6.4
- Total bilirubin should be < 1.5 times ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 1.5 times ULN
- Amylase < 1.5 times ULN
- Ammonia < 1.5 times ULN
Exclusion Criteria
- Allergy to valproic acid
- Current coexisting malignancy other than basal cell carcinoma
- Women of child-bearing potential who are pregnant or breastfeeding; additionally, patients that become pregnant while on study protocol will be discontinued immediately
- Active systemic infections, coagulation disorders or other major medical illnesses
- Patients taking tolbutamide, warfarin, zidovudine, benzodiazepines, clonazepam, diazepam
- Seizure disorder
- Patients with brain metastases
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01182285.
PRIMARY OBJECTIVES:
I. To determine if valproic acid will inhibit thyroid cancer growth, as evidenced by a decrease in thyroglobulin level, and tumor size.
II. To determine if valproic acid therapy will induce differentiation of thyroid cancer cells and therefore increase uptake of radioactive iodine by the tumor cells.
III. To determine the effect of valproic acid on differentiation markers of thyroid cancer and global gene expression in thyroid tumor tissue.
OUTLINE:
PHASE I: Patients receive valproic acid orally (PO) once daily (QD) on days 1-3 and twice daily (BID) on days 4-7 of week 1 and days 1-7 of weeks 2-10.
PHASE II: Patients with increased radioiodine uptake at week 10 continue valproic acid PO BID for weeks 11-16 and prepare for an ablation. Patients without increased radioiodine uptake at week 10 maintain valproic acid PO BID for weeks 11-16. Patients achieving response continue valproic acid treatment for up to 52 weeks.
After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationNCI - Center for Cancer Research
Principal InvestigatorElectron Kebebew
- Primary ID10-C-0041
- Secondary IDsNCI-2013-01456, P09554
- ClinicalTrials.gov IDNCT01182285