A Trial of Lenvatinib (E7080) in Subjects With Iodine-131 Refractory Differentiated Thyroid Cancer to Evaluate Whether an Oral Starting Dose of 18 Milligram (mg) Daily Will Provide Comparable Efficacy to a 24 mg Starting Dose, But Have a Better Safety Profile

Completed · Phase 2 · Has a placebo group

Conditions studied: Thyroid Cancer

In brief

This is a multicenter, randomized, double-blind study being conducted as a postmarketing requirement to the US Food and Drug Administration (FDA) to evaluate whether there is a lower starting dosage of lenvatinib 24 mg once daily (QD) that provides comparable efficacy but has a better safety profile in participants with radioiodine-refractory differentiated thyroid cancer RR-DTC with radiographic evidence of disease progression within the prior 12 months.

Key facts

Study ID

NCT02702388

Run by

Eisai Inc.

People needed

241

Starts

2017-06-08

Expected to finish

2020-09-10

Last updated by the study team

2021-11-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have histologically or cytologically confirmed diagnosis of one of the following differentiated thyroid cancer (DTC) subtypes:
• Papillary thyroid cancer (PTC)
• Follicular variant
• 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)
• Follicular thyroid cancer (FTC)
• Hurthle cell
• Clear cell
• Insular
• Measurable disease meeting the following criteria and confirmed by central radiographic review:
• At least 1 lesion of greater than or equal to (>=)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 that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) using computed tomography/magnetic resonance imaging (CT/MRI). If there is only 1 target lesion and it is a non-lymph node, it should have a longest diameter of >=1.5 cm.
• Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
• Participants must show evidence of disease progression within 12 months (an additional month will be allowed to accommodate actual dates of performance of screening scans, that is, within less than or equal to <=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.
• Participants must be Iodine-131 refractory/resistant as defined by at least one of the following:
• One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan.
• One or more measurable lesions that have progressed according to RECIST 1.1 within 12 months (an additional month will be allowed to accommodate actual dates of performance of screening scans, ie, within ≤13 months) after Iodine-131 therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or posttreatment scanning. These participants must not be eligible for possible curative surgery.
• Cumulative activity of Iodine-131 of greater than (>) 600 millicurie (mCi) or 22 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry.
• 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 steroids for one month.
• Participants must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be <=5.50 micro-international units per liter [mcIU/ML]). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH <0.50 mcIU/ML) and this dose may be changed concurrently upon starting study drug treatment.
• All chemotherapy or radiation-related toxicities must have resolved to Grade <2 severity per Common Terminology Criteria for Adverse Events (CTCAE v4.03), except alopecia and infertility.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1.
• Adequate renal function defined as calculated creatinine clearance >=30 mL/min per the Cockcroft and Gault formula.
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) >=1500/mm\^3 (>=1.5*10\^3/uL)
• Platelets >=100,000/mm\^3 (>=100*10\^9/L)

You may not qualify if…

• Anaplastic or medullary carcinoma of the thyroid.
• Diagnosed with meningeal carcinomatosis.
• Two or more prior vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted therapies or any ongoing treatment for RR-DTC other than TSH-suppressive thyroid hormone therapy.
• Prior treatment with lenvatinib.
• Participants who have received any anticancer treatment within 21 days or any investigational agent within 30 days (or 5 half-lives) prior to the first dose of study drug and should have recovered from any toxicity related to previous anticancer treatment. This does not apply to the use of TSH suppressive thyroid hormone therapy.
• Major surgery (example, laparotomy, thoracotomy or joint replacement) within 3 weeks prior to randomization or elective surgery scheduled to be performed during the study.
• Participants having >1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 g/24 h will be ineligible.
• Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of study drug.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebral vascular accident within 6 months of the first dose of study drug, or cardiac arrhythmia associated with hemodynamic instability.
• Prolongation of corrected QT interval (QTc) to >480 ms as demonstrated by a repeated electrocardiogram (ECG) or a clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (example, a repeated demonstration of a QTc interval >500 ms).
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Active infection (any infection requiring treatment).
• Active malignancy (except for DTC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
• Bleeding or thrombotic disorders.
• Known intolerance to study drug (or any of the excipients).
• Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
• Females who are pregnant or breastfeeding.

Where it is running

• Facility #1 — San Diego, California, United States
• Facility #1 — Torrance, California, United States
• Facility #1 — Washington D.C., District of Columbia, United States
• Facility #1 — Boston, Massachusetts, United States
• Facility #2 — Boston, Massachusetts, United States
• Facility #1 — Ann Arbor, Michigan, United States
• Facility #1 — Detroit, Michigan, United States
• Facility#2 — Morristown, New Jersey, United States
• Facility#1 — Summit, New Jersey, United States
• Facility #1 — The Bronx, New York, United States
• Facility #1 — Columbus, Ohio, United States
• Facility #1 — Portland, Oregon, United States
• Facility #2 — Philadelphia, Pennsylvania, United States
• Facility #1 — Philadelphia, Pennsylvania, United States
• Facility #1 — Seattle, Washington, United States
• Facility #1 — Darlinghurst, New South Wales, Australia
• Facility #1 — Saint Leonards, New South Wales, Australia
• Royal Brisbane and Women's Hospital — Brisbane, Queensland, Australia
• Facility#2 — Chermside, Queensland, Australia
• Facility #1 — Herston, Queensland, Australia
• Facility #1 — Melbourne, Victoria, Australia
• Facility #1 — Nedlands, Western Australia, Australia
• Facility #1 — Melbourne, Australia
• Facility #1 — Saint Leonards, Australia
• Facility#1 — La Jolla, California, United States

Full record on ClinicalTrials.gov

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