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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

Treatments: Drug: vorinostat

Study type: Interventional

Funder types: NIH

Identifiers

NCT00134043

NCI-2012-01468

04110

N01CM62207 (U.S. NIH Grant/Contract)

OSU-04110

NCI-6902

CDR0000439450

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Drug: vorinostat