Trial Information

Phase 2 of Sunitinib (Sutent) in Patients With Locally Advanced or Metastatic Anaplastic, Differentiated or Medullar Thyroid Cancer

The THYSU trial is a phase II trial of sunitinib (Sutent) in patients with locally advanced
or metastatic anaplastic, differentiated or medullary thyroid carcinoma.

Due to arguments showing that angiogenesis could be involved in progression of metastatic
thyroid carcinoma and to objective response during a phase I trial with sunitinib, it was
justified to evaluate in a prospective trial the efficacy of sunitinib in metastatic thyroid
carcinoma. Furthermore, the standard treatment of metastatic thyroid carcinoma when a
general treatment is to be prescribed is limited to radioiodine. When radioiodine becomes
ineffective, there is no standard treatment despite some usage of chemotherapy.

The objective of the trial is to determine the objective tumor response rate in patients
with locally advanced or metastatic anaplastic, differentiated or medullary thyroid
carcinoma treated with sunitinib, a secondary objective is to evaluate the safety of
sunitinib in these patients with thyroid carcinoma.

The treatment of sunitinib is the standard dosage and schedule. Sunitinib is given orally at
the dose of 50 mg daily for 28 days followed by 2 weeks of rest. Forthcoming cycles remain
identical. Modification of the dose may use a lower dose at 37.5 mg or 25 mg given daily on
the same schedule. All patients will receive repeated cycles of treatment until disease
progression, occurrence of unacceptable toxicity, withdrawal of patient consent, or other
withdrawal criteria are met. After discontinuation of treatment and the mandated 28-day
follow up, patients will be followed only in order to collect information on further
antineoplastic therapy and survival. In patients discontinuing treatment for reasons other
than disease progression, tumor assessment will continue until disease progression, or
initiation of other antineoplastic therapies.

The more frequent side effects are asthenia, mucositis, arterial hypertension, hand foot
syndrome and diarrhea. Other side effects have been reported including nausea, vomiting,
cutaneous events, decrease in left ventricular ejection fraction, neutropenia, and
thrombopenia.

The patients must meet all of the following inclusion criteria to be eligible for enrollment
into the trial:

- Patients must sign and date IRB/EC-approved informed consent.

- Age ≥ 18.

- Patients must have a life expectancy of at least 3 months and Karnofsky performance
status ≥ 70%

- Patients must have histologically confirmed TC

- Tumor disease must be progressive (evidence of disease progression within 6 months)

- Patients should not be candidates for surgical resection, external beam radiotherapy or
radioiodine, and patients must not have more than one previous systemic treatment for
cancer

- Patients must have measurable disease defined by RECIST criteria as at least one lesion
at least 2 cm in length by conventional CT techniques or at least 1 cm by spiral CT
scan.

- Resolution of all acute toxic effects of any prior treatment to NCI - CTCAE (version
3.0) grade < 1.

- Patients must have discontinued from radiation therapy at least 4 weeks before first
dose of study treatment and must have recovered from any toxic effects of treatment.

- Blood pressure < 140 / 90 mmHg

- Patients must have adequate organ function.

- Patients with reproductive potential must use medically acceptable contraceptive
method.

- Willingness and ability to comply with the study procedures.

- Patient affiliated with or profiting from a social security system

The presence of any non-inclusion criteria will exclude a patient from study enrollment.

Prior to undergoing any specific study procedures, patient and investigator sign informed
consent. During the initial visit including verification of eligibility criteria, an
interview with the patient is conducted regarding his/her recent and past clinical and
treatment history (including oncology history). Physical examination including examination
of major body systems, Karnofsky performance status, body weight, height, and vital signs is
performed. Laboratory data are collected (hematology and chemistry, coagulation, thyroid
tests, tumor markers and pregnancy test if applicable). Para clinic evaluations (12-lead
ECGs and tumor imaging) are carried out. LVEF assessed by Echocardiogram or by MUGA scan (if
necessary) and Brain Naturatic Peptide (Or NT pro-BNP) test are done.

During the follow-up, the patients are followed between the end of week 4 and week 6 by
clinical and biological evaluation. Evaluation of tumor sites under sunitinib is planned
every 2 cycles with CT scans. For patients with anaplastic or differentiated thyroid
carcinoma, the first stage will include 21 efficacy-evaluable patients. An additional 29
efficacy-evaluable patients will be included at the second stage.

For patients with medullary thyroid carcinoma, the first stage will include 11
efficacy-evaluable patients. An additional 7 to 14 efficacy-evaluable patients will be
included at the second stage.

10 French Oncology Departments are involved in this trial.