| Eligibility |
Inclusion criteria:
1. Participants must have histologically or cytologically confirmed diagnosis of one of
the following Differentiated Thyroid Cancer (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:
1. At least 1 lesion of = 1.0 centimeter (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 Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 using computerized 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 of = 1.5 cm.
2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies
such as radiofrequency (RF) ablation must show evidence of progressive disease
(substantial size increase of = 20%) to be deemed a target lesion.
3. Participants must show evidence of disease progression comparing (a) scan in screening
and (b) historical scan obtained within 12 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. Participants must not be eligible for possible curative surgery and must be
radioiodine (131 I)- refractory / resistant as defined by at least one of the
following:
1. One or more measurable lesions that do not demonstrate iodine uptake on any
radioiodine scan
2. 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.
3. Cumulative activity of 131 I of > 600 millicurie (mCi) or 22 gigabecquerels
(GBq), with the last dose administered at least 6 months prior to study entry
5. Participants may have received 0 or 1 prior vascular endothelial growth factor/
vascular endothelial growth factor receptor (VEGF/VEGFR)-targeted therapy (for example
sorafenib, sunitinib, pazopanib, etc.). Each of the VEGF/VEGFR targeted agents will be
counted individually, regardless of the duration of its administration.
6. Participants 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. Participants must be receiving thyroxine suppression therapy and thyroid stimulating
hormone (TSH) should be = 0.1 milliunits/Liter (mU/L) (= 0.5 mU/L if there is safety
concern).
8. All chemotherapy or radiation related toxicities must have resolved to < Grade 2
severity per Common Terminology Criteria for Adverse Events (CTCAE v 4.0), except
alopecia and infertility.
9. Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status
of 0 - 2.
10. Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as BP = 150/90 millimeter of mercury (mm Hg) at screening and no
change in antihypertensive medications within 1 week prior to Cycle 1/Day 1
11. Adequate renal function defined as calculated creatinine clearance
= 30 mL/min per the Cockcroft and Gault formula
12. Adequate bone marrow function:
1. Absolute neutrophil count (ANC) = 1500 per cubic meter (mm3) (= 1.5 × 10^3/micro
liter [µL])
2. Platelets = 100,000/mm3 (= 100 × 10^9/ liter [L])
3. Hemoglobin = 9.0 gram per deciliter (g/dL)
13. Adequate blood coagulation function as evidenced by an International Normalized Ratio
(INR) = 1.5
14. Adequate liver function:
1. Bilirubin = 1.5 × upper limit of normal (ULN) except for unconjugated
hyperbilirubinemia or Gilbert's syndrome
2. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) = 3 × ULN (= 5 × ULN if participant 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 human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25
international unit per liter (IU/L) or equivalent units of 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
(ie, 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 double-barrier 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 participant 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 participants must have had a successful vasectomy (confirmed azoospermia) or they
and their female partners must meet the criteria above (ie, 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
Exclusion criteria:
1. Anaplastic or medullary carcinoma of the thyroid
2. Two or more prior VEGF/VEGFR-targeted therapies or any ongoing treatment for 131
I-refractory DTC other than TSH-suppressive thyroid hormone therapy
3. Prior treatment with lenvatinib
4. Participants who have received any anticancer treatment (including Chinese herbal
medicine specified for the treatment of tumor) within 21 days or any investigational
agent within 30 days prior to the first dose of study drug. This does not apply to the
use of TSH-suppressive thyroid hormone therapy.
5. Major surgery within 3 weeks prior to the first dose of study drug
6. Participants having > 1 + proteinuria on urine dipstick testing (Participants with
urine protein < 1 g/24 hour (h) will be eligible).
7. Gastrointestinal malabsorption or any other condition that in the opinion of the
investigator might affect the absorption of lenvatinib
8. Significant cardiovascular impairment: history of (a) congestive heart failure greater
than New York Heart association (NYHA) Class II, (b) unstable angina, (c) myocardial
infarction, (d) stroke, or (e) cardiac arrhythmia associated with impairment within 6
months of the first dose of study drug
9. Prolongation of corrected Q wave and T wave (QTc) interval to > 480 millisecond (ms)
10. Bleeding or thrombotic disorders (Treatment with low molecular weight heparin [LMWH]
is allowed.)
11. Radiographic evidence of major blood vessel invasion/infiltration
12. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to
the first dose of study drug
13. Active infection (any infection requiring systemic treatment)
14. Active malignancy (except for DTC or definitively treated basal or squamous cell
carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past
24 months
15. Known intolerance to any of the study drugs (or any of the excipients)
16. Any medical or other condition which, in the opinion of the investigator, would
preclude participation in a clinical trial
17. Females who are pregnant or breastfeeding
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