Lenvatinib and Iodine Therapy in Treating Patients With Radioactive Iodine-Sensitive Differentiated Thyroid Cancer

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of lenvatinib pretreatment along with radioactive iodine (RAI) in
patients with previously treated RAI sensitive thyroid cancer.

SECONDARY OBJECTIVES:

I. To demonstrate the safety of the combination of lenvatinib and RAI in patients with Iodine
sensitive differentiated thyroid carcinoma (DTC).

II. To assess dynamic changes in established serum based biomarkers of DTC (thyroglobulin
[Tg] and Tg antibody).

III. To explore the utility of protein and genetic biomarkers to predict treatment efficacy.

OUTLINE:

Patients receive lenvatinib orally (PO) once daily (QD) for 8 weeks and up to 12 weeks in the
absence of disease progression or unaccepted toxicity. Patients also receive iodine I-131 PO
daily as standard of care.

After completion of study treatment, patients are followed up within 6 weeks, every 3 months
for 1 year, and then periodically thereafter.

Inclusion Criteria:

- Prior treatment with therapeutic dose of radioactive iodine (> 50 mCi) with evidence
of RAI uptake on delayed scan and with progression (biochemical or anatomic) within 12
months of RAI

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky ≥ 80%)

- Leukocytes ≥ 3,000/µL

- Absolute neutrophil count ≥ 1,500/µL

- Platelets ≥ 100,000/µL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
≤ 2.5 x institutional upper limit of normal

- Creatinine within normal institutional limits OR

- Creatinine clearance ≥ 60 mL/min/1.73 m² for patients with creatinine levels above
institutional normal

- Confirmed diagnosis of differentiated thyroid cancer (follicular or papillary thyroid
cancer and their variants)

- Ability and willingness to use appropriate contraception; women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry and for the duration of study
participation; should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately; men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and for 2
weeks after completion of lenvatinib administration

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray
or as ≥ 10 mm (≥ 1 cm) with computed tomography (CT) scan, magnetic resonance imaging
(MRI), or calipers by clinical exam

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have received RAI within 12 weeks of planned retreatment

- Prior receipt of cumulative RAI doses in excess of 1000 mCi

- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1)

- Patients who are receiving any other investigational agents

- Patients with previously untreated and or symptomatic brain metastases are excluded
from this clinical trial because of the risk of intracranial bleeding with angiogenic
agents and tumoral swelling from RAI

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lenvatinib

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Patients with uncontrolled hypertension (requirement for more than 2 blood pressure
[BP] medications or grade 2 or higher BP elevation while on adequate doses of not more
than 2 antihypertensive agents) are excluded from the study because one of the
significant adverse events of lenvatinib is worsening hypertension

- Fridericia's corrected QT (QTcF) interval prolongation greater than 500 ms

- Recent arterial thromboembolic event within the previous 6 months

- Urine dipstick proteinuria ≥ 2+ or nephrotic range proteinuria on ≥ 2 gram in 24-hour
urine

- History of gastrointestinal perforation, abscess or fistula

- History of and or medical condition (e.g. diverticular disease; aneurysm) that
predisposes to risk of major hemorrhage

- Pregnant women are excluded from this study because lenvatinib is a tyrosine kinase
inhibitor agent with the potential for teratogenic or abortifacient effects; because
there is an unknown but potential risk for adverse events in nursing infants secondary
to treatment of the mother with lenvatinib, breastfeeding should be discontinued if
the mother is treated with lenvatinib

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
lenvatinib