• Response rate as measured by RECIST criteria at 8 weeks [ Designated as safety issue: No ]
  
• Disease stabilization rate as measured by RECIST criteria at 6 months [ Designated as safety issue: No ]
  

• Radioactive iodine avidity as measured by diagnostic whole body scan at 8 weeks following study treatment [ Designated as safety issue: No ]
  
• Serum thyroglobulin at 8 weeks following study treatment [ Designated as safety issue: No ]
  
• Fludeoxyglucose F 18 (FDG) avidity as measured by FDG-positron emission tomography scan at 8 weeks following study treatment [ Designated as safety issue: No ]
  
• Na+/I- symporter expression as measured by immunohistochemistry and reverse transcription polymerase chain reaction at 8 weeks following study treatment [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the antitumor activity of FR901228 (depsipeptide), in terms of the proportion of patients achieving a complete or partial response or disease stabilization, in patients with progressive recurrent and/or metastatic non-medullary thyroid carcinoma that is refractory to radioactive iodine (RAI).
• Determine the safety and tolerability of this drug in these patients.

Secondary

• Document changes in RAI uptake by comparing pre- and post-treatment RAI scans in patients treated with this drug.
• Determine post-treatment changes in serum thyroglobulin in patients treated with this drug.
• Correlate changes in post-treatment positron-emission tomography scans with whole-body RAI scans in patients treated with this drug.

OUTLINE: Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 10.5-20.5 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-medullary thyroid carcinoma, including the following cell types:

  • Papillary
  • Follicular
  • Variants of papillary or follicular
  • Hürthle cell
• Recurrent and/or metastatic disease

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Progressive disease during or after prior treatment, as defined by ≥ 1 of the following criteria:

  • Presence of new or progressive lesions on CT scan or MRI
  • New lesions on bone or positron-emission tomography scan

  • Rising thyroglobulin level

    • Minimum of 3 consecutive rises with an interval of ≥ 1 week between each determination

• Refractory to radioactive iodine (RAI)

  • Absent or insufficient RAI-uptake* documented by whole-body RAI scan within the past 6 months

    • At least 1 lesion with absent RAI-uptake required for insufficient uptake NOTE: *Insufficient uptake defined as "faint" or "minimal" based on independent assessment by 2 observers from either endocrinology or nuclear medicine
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,00/mm^3

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Chronic active viral hepatitis allowed provided patient is clinically stable and fulfills liver function eligibility criteria

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• QTc ≤ 480 msec by ECG
• ST segment depression < 2 mm
• LVEF ≥ 50 % by echocardiogram
• No left ventricular hypertrophy, as defined by end-diastolic wall thickness > 12 mm in both the left ventricular posterior wall as well as septum or restrictive cardiomyopathy

• No history of any of the following cardiac diseases:

  • Canadian Cardiovascular Society (CCS) class II-IV angina pectoris
  • Myocardial infarction within the past 12 months
  • Sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator
  • Any cardiac arrhythmia requiring digitalis or another antiarrhytmic medication other than a beta blocker or calcium channel blocker
  • No uncontrolled hypertension (i.e., blood pressure ≥ 160/95)

  • Mobitz II second degree block in patients who do not have a pacemaker

    • First degree or Mobitz I second degree block, bradyarrhythmias or sick sinus syndrome require Holter monitoring and evaluation by cardiology
  • Uncontrolled dysrhythmias
• No history of congenital long QT syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Thyroid stimulating hormone normal or suppressed
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to FR901228
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior biologic or targeted agents (e.g., interferon alfa, thalidomide, octreotide, or cetuximab)
• No concurrent antineoplastic biologic agents

Chemotherapy

• No prior FR901228 (depsipeptide)

• No prior cytotoxic chemotherapy

  • Cytotoxic chemotherapy as a radiosensitizer allowed provided ≥ 3 months since prior administration
• No other concurrent antineoplastic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• See Chemotherapy

• At least 4 weeks since prior external beam radiation therapy

  • Documented disease progression required if patient received external beam radiotherapy to index lesions

• At least 3 months since prior RAI therapy

  • Diagnostic studies using ≤ 12 mCi of RAI are not considered RAI therapy
• No concurrent antineoplastic radiotherapy

Surgery

• Not specified

Other

• At least 2 weeks since prior anticancer cyclooxygenase-2 (COX-2) inhibitors, isotretinoin, or complementary medications
• At least 4 weeks since prior tyrosine kinase inhibitors (e.g., gefitinib or erlotinib)
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent drugs known to have histone deacetylase inhibitor activity (e.g., valproic acid)
• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No concurrent hydrochlorothiazide
• No concurrent treatment dose warfarin
• No concurrent agents that cause QTc prolongation
• Concurrent daily aspirin given after myocardial infarction or COX-2 inhibitors at standard anti-inflammatory or pain doses allowed