| Inclusion Criteria: | 1) Subjects must have histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: a. Papillary thyroid cancer (PTC) i. Follicular variant ii. Variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated) b. Follicular thyroid cancer (FTC) i. Hürthle cell ii. Clear cell iii. Insular
2) Measurable disease meeting the following criteria and confirmed by central radiographic review: a. At least one lesion of >/= 1.0 cm in the longest diameter for a non-lymph node or >/= 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computed tomography / magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter or >/=1.5cm. b. Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
3) Subjects must show evidence of disease progression within 12 months (an additional month will be allowed to accommodate actual dates of performance of scans, i.e., within </=13 months) prior to signing informed consent, according to RECIST 1.1 assessed and confirmed by central radiographic review of CT and / or MRI scans
4) Subjects must be 131^I-refractory / resistant as defined by at least one of the following : a. One or more measurable lesions that do not demonstrate 131^I uptake on any radioiodine scan b. One or more measurable lesions that has progressed by RECIST 1.1 within 12 months of 131^I therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning These subjects must not be eligible for possible curative surgery. c. Cumulative activity of 131^I of > 600 mCi or 22 gigabequerels (GBq), with the last dose administered at least 6 months prior to study entry
5) Subjects may have received 0 or 1 VEGF/VEGFR-targeted therapy (ex: sorafenib, sunitinib, pazopanib, etc.)
6) Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for one month
7) Subjects must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be </= 5.50 mcu/mL). When tolerated by the subject, thyroxine dose should be changed to achieve TSH suppression (TSH < 0.50 mcu/mL) and this dose can be changed concurrently upon starting E7080
8) All chemotherapy or radiation-related toxicities must have resolved to < Grade 2 severity per CTCAE criteria v 4.0, except alopecia and infertility.
9) Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2
10) Adequately controlled blood pressure with or without antihypertensive medications, defined as BP =/< 150/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit
11) Adequate renal function defined as calculated creatinine clearance >/= 30 mL/min per the Crockcroft and Gault formula
12) Adequate bone marrow function: a. Absolute neutrophil count (ANC) >/= 1500/mm^3 (>/=1.5 × 10^3/μL); b. Platelets >/= 100,000/mm^3 (>/= 100 × 10^9/L); c. Hemoglobin >/= 9.0 g/dL.
13) Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) </= 1.5
14) Adequate liver function: a. Bilirubin </= 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome; b. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) </= 3 × the ULN (</= 5 × ULN if subject has liver metastases).
15) Males or females age >/= 18 years at the time of informed consent
16) Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta human chorionic gonadotropin test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
17) All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
18) Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a doublebarrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation
19) Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation) Those with partners using hormonal contraceptives must also be using an additional approved method of contraception, as described previously.
20) Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol. |