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

Phase 2

Completed

Conditions: Recurrent Thyroid Cancer
Stage IV Follicular Thyroid Cancer
Stage IV Papillary Thyroid Cancer

Interventions: Drug: romidepsin
Other: laboratory biomarker analysis
Procedure: positron emission tomography

Registration Number: NCT00098813

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well romidepsin works in treating patients with recurrent and/or metastatic thyroid cancer that has not responded to radioactive iodine. Romidepsin may stop the growth of tumor cells by blocking the some of the enzymes needed for cell growth. It may also help radioactive iodine and chemotherapy work better by making tumor cells more sensitive to the drug

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (romidepsin)	romidepsin	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.
Treatment (romidepsin)	laboratory biomarker analysis	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.
Treatment (romidepsin)	positron emission tomography	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.

Primary Outcome Measures