Clinical trial NCT00134043: Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer
Official title: Phase II Study of Histone Deacetylase Inhibitor SAHA (Vorinostat) in Patients With Metastatic Thyroid Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-08-24
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective Response Rate (PR + CR) Using RECIST/WHO Response Criteria
timeFrame: Up to 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Manisha Shah
role: PRINCIPAL_INVESTIGATOR
References:
citation: Woyach JA, Kloos RT, Ringel MD, Arbogast D, Collamore M, Zwiebel JA, Grever M, Villalona-Calero M, Shah MH. Lack of therapeutic effect of the histone deacetylase inhibitor vorinostat in patients with metastatic radioiodine-refractory thyroid carcinoma. J Clin Endocrinol Metab. 2009 Jan;94(1):164-70. doi: 10.1210/jc.2008-1631. Epub 2008 Oct 14.