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

Phase 2

Completed

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

Interventions: Drug: vorinostat

Registration Number: NCT00134043

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	vorinostat	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (PR + CR) Using RECIST/WHO Response Criteria	Up to 3 years	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.

Secondary Outcome Measures