Phase II Study of Histone Deacetylase Inhibitor SAHA (Vorinostat) in Patients With Metastatic Thyroid Carcinoma
Phase II Study of Histone Deacetylase Inhibitor SAHA (Vorinostat) in Patients With Metastatic Thyroid Carcinoma
This phase II trial is studying how well suberoylanilide hydroxamic acid works in treating patients with metastatic and/or locally advanced or locally recurrent thyroid cancer. Drugs used in chemotherapy, such as suberoylanilide hydroxamic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Suberoylanilide hydroxamic acid may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. Determine the objective response rate in patients with metastatic and/or locally advanced or locally recurrent thyroid cancer treated with suberoylanilide hydroxamic acid.
SECONDARY OBJECTIVES:
I. Determine the toxicity of this drug in these patients.
OUTLINE:
Patients receive oral suberoylanilide hydroxamic acid (SAHA) twice daily on days 1-14. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are then evaluated for disease response. Patients achieving a complete response receive an additional 2 courses of SAHA. Patients achieving stable disease or a partial response receive 4 additional courses of SAHA. After completion of study treatment, patients are followed within 4 weeks.
Inclusion Criteria:
Histologically confirmed thyroid cancer
One of the following subtypes:
Metastatic and/or locally advanced or locally recurrent disease
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
Lesions in a previously irradiated area allowed provided there has been subsequent disease progression of the irradiated lesions
The following are not considered measurable disease:
Not a candidate for radioactive iodine I^131 therapy
Performance status - ECOG 0-1
At least 6 months
WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1.5 mg/dL
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine ≤ 1.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drug
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No other uncontrolled illness
No other active malignancy except nonmetastatic nonmelanoma skin cancer or carcinoma in situ of the cervix
More than 4 weeks since prior systemic cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin)
No more than 2 prior chemotherapy regimens for the treatment of thyroid cancer
See Disease Characteristics
More than 4 weeks since prior external beam radiotherapy
At least 24 weeks since prior radioactive iodine I^131 therapy
Recovered from prior therapy
More than 4 weeks since prior valproic acid or any other histone deacetylase inhibitor
More than 4 weeks since prior investigational tumor-specific therapy
Concurrent oral or IV bisphosphonates for bony metastases allowed at the discretion of the investigator
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent tumor-specific or investigational therapy
No other concurrent anticancer therapy
No concurrent adjuvant therapy for another cancer