This Expanded Access Program (EAP) consists of a Prerandomization Phase and aRandomization Phase. Only subjects with radioiodine-refractory DTC who fulfill theeligibility criteria will be treated. These subjects will be treated until progression ofdisease or unacceptable toxicity.
Drug: Lenvatinib
Lenvatinib at starting doses of 24-mg, 20-mg, or 14-mg will be administered as a
combination of 10-mg capsules and 4-mg capsules to be taken once a day (QD) (recommended
to be taken the same time each day). Subjects will receive one of three starting doses of
lenvatinib, 24-mg/day, 20-mg/day, or 14-mg/day. Dose reductions occur in succession based
on the previous dose level (24, 20, 14, and 10 mg/day). Any dose reduction below 10
mg/day must be discussed with the sponsor. Once the dose has been reduced, it cannot be
increased at a later date.
Other Name: E7080
Inclusion Criteria
1. Subjects must have histologically or cytologically confirmed diagnoses 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, Hurthle cell variant of papillary carcinoma, poorly
differentiated); b.Follicular thyroid cancer (FTC) i. Hurthle cell ii. Clear cell
iii.Insular
2. Subjects must be radioiodine-refractory or resistant within 12 months of radioiodine
therapy and have one of the following:
1. One or more lesions that do not demonstrate iodine uptake on any radioiodine
scan
2. One or more lesions that have substantially increased in size within 12 months
of radioiodine therapy, despite demonstration of radioiodine activity at the
time of that treatment by pre- or posttreatment scanning
3. Cumulative activity of radioiodine of greater than 600 mCi or 22 gigabecquerels
(GBq), with the last dose administered at least 6 months prior to study entry
3. Subjects must have received and failed treatment with sorafenib for RR-DTC. This
criterion will not apply outside the United States if sorafenib is not commercially
available in the country where the subject resides.
4. ECOG performance status of 0 to 2
5. Blood pressure (BP) less than or equal to 150/90 mmHg at screening with or without
antihypertensive medications and no change in antihypertensive medications within 1
week prior to Cycle 1 Day 1
6. Creatinine clearance greater than or equal to 30 mL/min according to the Cockcroft
and Gault formula
7. Adequate bone marrow function
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
- Hemoglobin greater than or equal to 9.0 g/dL (can be corrected by growth factor
or transfusion)
- Platelet count greater than or equal to 100 x 10^9/L
8. Adequate liver function
- Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) except for
unconjugated hyperbilirubinemia or Gilbert's syndrome
- Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) less than or equal to 3 x ULN (less than or equal to 5 x
ULN if subject has liver metastases). If ALP is greater than 3 x ULN (in the
absence of liver metastases) or greater than 5 x ULN (in the presence of liver
metastases) AND subjects are also known to have bone metastases, the
liver-specific ALP must be separated from the total and used to assess the
liver function instead of the total ALP
9. Provide written informed consent
10. Males and females age greater than or equal to 18 years at the time of informed
consent
11. All females must have a negative serum or urine pregnancy test. Females of
childbearing potential and male subjects who are partners of women of childbearing
potential must use or their partners must use a highly effective method of
contraception
Exclusion Criteria
1. Subjects having greater than 1+ proteinuria on urine dipstick at screening testing
will undergo 24 h urine collection for quantitative assessment of proteinuria.
Subjects with urine protein greater than or equal to 1 g/24 h will be ineligible.
2. History of congestive heart failure with New York Heart Association (NYHA)
Classification greater than II, unstable angina, myocardial infarction, serious
cardiac arrhythmia, or stroke within the past 6 months
3. Electrocardiogram (ECG) with QT interval (QTc) interval greater than or equal to 480
msec
4. Existing anti-cancer therapy-related toxicities of grade greater than or equal to 2,
except alopecia and infertility
5. History of intolerance to or progression on prior treatment with lenvatinib that led
to the discontinuation of lenvatinib
6. Any history of or concomitant medical condition that, in the opinion of the
investigator, would compromise subject's ability to safely complete the protocol
7. Females who are pregnant (positive B-hCG test) or breastfeeding
8. Eligible for any other lenvatinib study that is open for recruitment.
La Jolla, California, United States
Stanford, California, United States
Torrance, California, United States
Washington, District of Columbia, United States
Chicago, Illinois, United States
Boston, Massachusetts, United States
Lansing, Michigan, United States
Lebanon, New Hampshire, United States
Neptune, New Jersey, United States
Cleveland, Ohio, United States
Portland, Oregon, United States
Philadelphia, Pennsylvania, United States
Houston, Texas, United States