Romidepsin in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Has Not Responded to Radioactive Iodine

PRIMARY OBJECTIVES:

I. Determine the antitumor activity of romidepsin (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).

II. Determine the safety and tolerability of this drug in these patients.

SECONDARY OBJECTIVES:

I. Document changes in RAI uptake by comparing pre- and post-treatment RAI scans in patients treated with this drug.

II. Evaluate changes in the expression of the Na+/I- symporter (NIS) in tumors, as measured by immunohistochemistry on pre- and post-treatment biopsy specimens; and real time reverse transcriptase polymerase chain reaction (RT-PCR) for NIS mRNA on pre- and post-treatment changes biopsy specimens.

III. Determine post-treatment changes in serum thyroglobulin in patients treated with this drug.

IV. Correlate changes in post-treatment positron-emission tomography scans with whole-body RAI scans in patients treated with this drug.

OUTLINE:

Patients receive romidepsin 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.

Inclusion criteria

• 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
• No known brain metastases
• Performance status - Karnofsky 60-100%
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,00/mm^3
• 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
• Creatinine normal
• Creatinine clearance >= 60 mL/min
• 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 antiarrhythmic 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
• 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
• At least 4 weeks since prior biologic or targeted agents (e.g., interferon alfa, thalidomide, octreotide, or cetuximab)
• No concurrent antineoplastic biologic agents
• 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
• Not specified
• 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
• 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