An Open-label, Multicenter, Phase II Study of Dovitinib in Advanced Thyroid Cancer
An Open-label, Multicenter, Phase II Study of Dovitinib in Advanced Thyroid Cancer
There has been no effective treatment for advanced thyroid cancer that is not amenable to
 surgery and that does not concentrate iodine. Response rates with chemotherapy have been so
 low that best supportive care has been the standard of care for most patients. In recent
 phase I and phase II clinical studies, dovitinib has shown activity as a single agent in
 solid tumors. Therefore, we will conduct a phase II, single-arm trial to determine the
 efficacy of dovitinib in radioactive iodine-refractory recurrent or metastatic thyroid
 cancer.
Inclusion Criteria:

 -  Histologically proven diagnosis of thyroid cancer (papillary, follicular/Hürthle cell
 variant, medullary)

 -  Patients with metastatic or unresectable thyroid cancer for which curative measures
 (surgical resection, external-beam radiation therapy, or radioactive iodine) were no
 longer effective

 -  Documented evidence of disease progression (based on radiographic imaging), according
 to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, within 6 months
 before entry into the study for papillary follicular/Hürthle cell variant

 -  Prior therapy with surgery, 131I treatment, chemotherapy, radiotherapy will be
 allowed, but not within 3 weeks of treatment.

 -  Patients who received a prior biologic treatment (kinase inhibitor, vaccine or
 antibody-based therapy), except prior VEGFR/FGFR inhibitor therapy, can be allowed
 after 3 weeks of treatment.

 -  Patients must have at least one measurable lesion, which has not been externally
 irradiated, as defined by RECIST criteria version 1.1

 -  Age : 20-90

 -  Performance status of Eastern Cooperative Oncology Group 0 to 2

 -  Life expectancy > 3 months

 -  Adequate bone marrow function: ANC≥1,500/uL, hemoglobin≥9.0 g/dL (can be corrected by
 transfusion) and platelet≥100,000/uL

 -  Adequate renal function (creatinine<1.5 mg/dL)

 -  Adequate liver function (total bilirubin <1.5 x ULN, trans-aminase <3 x ULN)

 -  Adequate blood glucose and lipid level (at fasting cholesterol < 2xUNL, triglyceride <
 2xUNL, HbA1c < 9%)

 -  Patient compliance and geographic proximity that allow adequate follow up

 Exclusion Criteria:

 -  Patients with CNS metastases

 -  Patients with another primary malignancy within 3 years prior to starting study drug,
 with the exception of adequately treated in-situ carcinoma of the uterine cervix, or
 skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or
 non-melanomatous skin cancer)

 -  Patients who have received the last administration of an anticancer therapy including
 chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding
 nitrosurea, mitomycin-C, targeted therapy and radiation) ≤ 4 weeks prior to starting
 study drug, or who have not recovered from the side effects of such therapy

 -  Patients who have received the last administration of nitrosurea or mitomycin-C ≤ 6
 weeks prior to starting study drug, or who have not recovered from the side effects of
 such therapy

 -  Patients who have received targeted therapy (e.g. sunitinib, sorafenib, pazopanib) ≤ 2
 weeks prior to starting study drug, or who have not recovered from the side effects of
 such therapy

 -  Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2
 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for
 analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered
 from radiotherapy toxicities

 -  Pregnant or breast-feeding women

 -  Fertile males not willing to use contraception, as stated above

 -  Patients unwilling or unable to comply with the protocol