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Phase II Trial of Sunitinib (SU11248) in Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers and Medullary Thyroid Cancers

Phase 2
18 Years
Open (Enrolling)
Papillary Thyroid Cancer, Recurrent Thyroid Cancer, Stage III Follicular Thyroid Cancer, Stage IVA Follicular Thyroid Cancer, Stage IVA Papillary Thyroid Cancer, Stage IVB Follicular Thyroid Cancer, Stage IVB Papillary Thyroid Cancer, Stage IVC Follicular Thyroid Cancer, Stage IVC Papillary Thyroid Cancer, Thyroid Gland Medullary Carcinoma

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Trial Information

Phase II Trial of Sunitinib (SU11248) in Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers and Medullary Thyroid Cancers


I. Determine the response rate to sunitinib (sunitinib malate) in patients with
iodine-refractory, unresectable well-differentiated thyroid cancer (WDCT) or medullary
thyroid cancer (MTC) who have evidence of disease progression within the past 6 months.

II. Determine the toxicity of this drug in these patients. III. Determine the duration of
response, progression-free survival, and overall survival of patients with WDTC or MTC
treated with this drug.

IV. Determine whether the presence of RET gene rearrangements in patients with WDTC or RET
mutations in patients with MTC predict response to sunitinib.

V. Determine whether therapy with sunitinib affects phosphorylation of downstream RET
effector, ERK, in WDTC and MTC tissue.

VI. Determine whether specific germ-line polymorphisms in the RET gene are associated with
favorable outcome in patients with WDTC treated with sunitinib.

OUTLINE: This is an open-label, parallel-group, cohort, multicenter study. Patients are
assigned to 1 of 2 cohorts according to type of thyroid cancer (medullary vs

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6
weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 2 years.

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of 1 of the following:

- Well-differentiated thyroid carcinoma (WDTC), including any of the following

- Papillary

- Follicular

- Hürthle cell

- Medullary thyroid carcinoma (MTC)

- Must show evidence of disease progression within the past 6 months despite treatment
with iodine I 131 therapy OR ineligible for iodine I 131 therapy

- Unresectable disease

- Patients with WDTC must be receiving thyroxine suppression therapy

- Measurable disease meeting 1 of the following criteria:

- Radiographically measurable disease defined as ≥ 1 lesion that can be accurately
measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques or as ≥ 10 mm by
spiral CT scan

- Biochemically measurable disease defined as an elevated thyroglobulin (WDTC
patients) or calcitonin (MTC patients)

- No known brain metastases

- Patients with brain metastases with stable neurologic status after local therapy
(surgery or radiotherapy) for ≥ 8 weeks from definitive therapy and without
neurologic dysfunction that would confound the evaluation of neurologic and
other adverse events are eligible

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Calcium ≤ 12.0 mg/dL

- Bilirubin normal

- AST or ALT ≤ 2.5 times upper limit of normal (ULN) (or ≤ 5.0 times ULN if patient has
liver metastases)

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to sunitinib malate

- No poorly controlled hypertension, defined as systolic blood pressure (BP) ≥ 140 mm
Hg or diastolic BP ≥ 90 mm Hg

- No condition that would impair ability to swallow and retain sunitinib malate
tablets, including any of the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement of IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- No serious or nonhealing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No pulmonary embolism within the past 12 months

- QTc < 500 msec

- No significant ECG abnormalities

- No cerebrovascular accident or transient ischemic attack within the past 12 months

- No myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic
congestive heart failure, or coronary or peripheral artery bypass graft or stenting
within the past 12 months

- No New York Heart Association (NYHA) class III-IV heart failure or other condition

- No serious ventricular arrhythmia (i.e., ventricular fibrillation or ventricular
tachycardia ≥ 3 beats in a row)

- Patients with any of the following conditions must have NYHA class II cardiac
function confirmed on baseline ECHO/MUGA scan

- History of class II heart failure and asymptomatic on treatment

- Prior anthracycline exposure

- Received central thoracic radiation that included the heart in the radiotherapy

- No uncontrolled intercurrent illness, including, but not limited to, any of the

- Ongoing or active infections

- Psychiatric illness or social situation that would preclude study compliance

- Recovered from prior therapy

- No more than 1 prior chemotherapy regimen for metastatic disease

- No prior external-beam radiation to the measured tumor constituting the target

- No prior receptor tyrosine kinase inhibitors

- No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171,
vatalanib, VEGF Trap)

- At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas
or mitomycin C)

- At least 4 weeks since prior major surgery

- No other concurrent anticancer agents or therapies

- No other concurrent investigational agents

- No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as

- Doses ≤ 2 mg daily for prophylaxis of thrombosis allowed

- Low molecular weight heparin allowed provided PT INR ≤ 1.5

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent enzyme-inducing anticonvulsants

- No concurrent agents with proarrhythmic potential, including any of the following:

- Terfenadine

- Quinidine

- Procainamide

- Disopyramide

- Sotalol

- Probucol

- Bepridil

- Haloperidol

- Risperidone

- Indapamide

- Flecainide

- At least 7 days since prior and no concurrent inhibitors of CYP3A4, including any of
the following:

- Azole antifungals (e.g., ketoconazole, itraconazole)

- Clarithromycin, erythromycin

- Diltiazem

- Verapamil

- HIV-protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir,

- Delavirdine

- At least 12 days since prior and no concurrent inducers of CYP3A4, including any of
the following:

- Rifampin

- Rifabutin

- Carbamazepine

- Phenobarbital

- Phenytoin

- Hypericum perforatum (St. John's wort)

- Efavirenz

- Tipranavir

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate

Outcome Description:

Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) if measurable disease is present or by a 50% decrease in the respective serum marker (thyroglobulin in cohort A and calcitonin in cohort B documented on at least 2 occasions, at least 4 weeks apart). All of the patients who met the eligibility criteria (with the possible exception of those who received no study medication) will be included in the main analysis of the response rate.

Outcome Time Frame:

Every 12 weeks, assessed up to 2 years

Safety Issue:


Principal Investigator

Ezra Cohen

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

Related Keywords:

  • Papillary Thyroid Cancer
  • Recurrent Thyroid Cancer
  • Stage III Follicular Thyroid Cancer
  • Stage IVA Follicular Thyroid Cancer
  • Stage IVA Papillary Thyroid Cancer
  • Stage IVB Follicular Thyroid Cancer
  • Stage IVB Papillary Thyroid Cancer
  • Stage IVC Follicular Thyroid Cancer
  • Stage IVC Papillary Thyroid Cancer
  • Thyroid Gland Medullary Carcinoma
  • Carcinoma
  • Thyroid Neoplasms
  • Thyroid Diseases
  • Adenocarcinoma, Follicular
  • Carcinoma, Medullary



University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
M D Anderson Cancer Center Houston, Texas  77030