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A Phase II Study of Single Agent Depsipeptide (FK228) in Radioiodine (RAI)-Refractory Metastatic Non-medullary (Papillary, Follicular, and Hurthle Cell Variants) Thyroid Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Recurrent Thyroid Cancer, Stage IV Follicular Thyroid Cancer, Stage IV Papillary Thyroid Cancer

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Trial Information

A Phase II Study of Single Agent Depsipeptide (FK228) in Radioiodine (RAI)-Refractory Metastatic Non-medullary (Papillary, Follicular, and Hurthle Cell Variants) Thyroid Carcinoma


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor major response rate (including stable disease) as measured by RECIST criteria

Outcome Time Frame:

8 weeks

Safety Issue:

No

Principal Investigator

David Pfister

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center at Suffolk

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01458

NCT ID:

NCT00098813

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Recurrent Thyroid Cancer
  • Stage IV Follicular Thyroid Cancer
  • Stage IV Papillary Thyroid Cancer
  • Thyroid Neoplasms
  • Thyroid Diseases
  • Adenocarcinoma, Follicular

Name

Location

Memorial Sloan-Kettering Cancer Center at SuffolkCommack, New York  11725