Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Study of Histone Deacetylase Inhibitor SAHA (Vorinostat) in Patients With Metastatic Thyroid Carcinoma

Conditions
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Insular Thyroid Cancer, Recurrent Thyroid Cancer, Stage II Follicular Thyroid Cancer, Stage II Papillary Thyroid Cancer, Stage IV Follicular Thyroid Cancer, Stage IV Papillary Thyroid Cancer, Thyroid Gland Medullary Carcinoma

Intervention / Treatment
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* Drug: vorinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed thyroid cancer One of the following subtypes: Papillary thyroid cancer Follicular thyroid cancer Hürthle cell thyroid cancer Insular thyroid cancer Medullary thyroid cancer Mixed histology thyroid cancer Poorly differentiated thyroid cancer Tall-cell thyroid cancer 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: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: vorinostat<br>* Given orally<br>* Other names: Zolinza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (PR + CR) Using RECIST/WHO Response Criteria | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR., or similar definition that is accurate and appropriate. | Up to 3 years |