Thyroid Cancer Clinical Trials

• Histologically confirmed DTC, defined as papillary, follicular, or Hurthle Cell thyroid cancer. Papillary has several sub-types such as tall-cell and columnar cell, which are all allowed.

• Patient must have incurable RAIR DTC, defined as disease not amenable to cure by surgery AND meeting one or more of the following criteria:

‣ one or more sites of disease that do not take up RAI.

⁃ disease progression on RAI (given within the last 12 months).

⁃ receipt of cumulative dose of RAI of ≥ 600mCi.

⁃ patient declines or is ineligible for surgery and/or RAI.

• Measurable or evaluable disease per RECIST 1.1.

• No more than 1 prior line of VEGF/VEGFR targeted therapy for DTC. Examples of VEGF/VEGFR therapies include sorafenib, pazopanib, vandetinib, axitinib, sunitinib, and cabozantinib, but others exist.

• Symptomatic (defined by usual standard of care clinical criteria) or progressive disease on most recent prior treatment (ex: surgery, RAI, or TKI/targeted therapy) by RECIST 1.1 over the last 16 months.

• At least 18 years of age.

• ECOG performance status ≤ 2.

• Screening blood pressure measurement \<140/90. Retesting is allowed.

• Adequate bone marrow and organ function as defined below:

‣ Absolute neutrophil count ≥ 1.0 K/cumm

⁃ Platelets ≥ 100 K/cumm

⁃ Hemoglobin ≥ 9.0 g/dL

⁃ Total bilirubin ≤ 1.5 x IULN

⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN (5.0 x IULN in the presence of hepatic metastases)

⁃ Creatinine clearance \> 30 mL/min by Cockcroft-Gault

⁃ UPC ≤ 1000 mg/G

⁃ QTcF \< 481 msec

• The effects of lenvatinib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of lenvatinib. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.

• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

• Measurable or evaluable disease per RECIST 1.1.

• Symptomatic (defined by usual standard of care clinical criteria) or progressive disease by RECIST 1.1 while on lenvatinib.

• ECOG performance status ≤ 2.

• Re-screening blood pressure measurement \<140/90.

• Adequate bone marrow and organ function as defined below:

‣ Absolute neutrophil count ≥ 1.0 K/cumm

⁃ Platelets ≥ 100 K/cumm

⁃ Hemoglobin ≥ 9.0 g/dL

⁃ Total bilirubin ≤ 1.5 x IULN

⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN (5.0 x IULN in the presence of hepatic metastases)

⁃ Creatinine clearance \> 30 mL/min by Cockcroft-Gault

⁃ UPC ≤ 1000 mg/G

⁃ QTcF \< 481 msec

• The most recent dose level of lenvatinib must be 10 mg/day.