A Study to Evaluate the Safety and Efficacy of Lenvatinib in Participants With Refractory Differentiated Thyroid Cancer

NCT03573960 | Completed Phase 4

• 1 other identifier: E7080-M091-507
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the safety of lenvatinib in participants with recurrent, metastatic radio-iodine refractory differentiated thyroid cancer (DTC).

Conditions

Thyroid Neoplasms

Keywords

Lenvatinib, E7080, Refractory Differentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with Grade 2 or Higher Treatment-emergent Adverse Events

  TEAEs are defined as undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment. Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activity of daily living (ADL), grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL, grade 4: Life-threatening consequences; urgent intervention indicated and grade 5: Death related to AE.

  Baseline up to Week 24

• Number of Dose Reductions

  The number of instances of participants having to reduce the dosage of study drug based on specified toxicities.

  Baseline up to Week 24

• Median Time to First Dose Reduction

  Time to first dose reduction is defined as the time period from the first dose to the first dose reduction. Median time taken for the first dose reduction and 95% confidence interval will be calculated and reported.

  Baseline up to Week 24

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Week 24

• Progression-free Survival (PFS)

  From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurs first) or up to approximately Week 24

• Percentage of Participants with Other TEAEs Below Grade 2

  Baseline up to Week 24

Study Arms (1)

Lenvatinib 24 mg

EXPERIMENTAL

Participants will receive 24 mg (two 10-mg capsules + one 4-mg capsule) orally, once daily with or without food in 28-day cycles until disease progression or until unacceptable toxicity occurs.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib capsules.

Lenvatinib 24 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females who are diagnosed with locally Recurrent or Metastatic, Progressive, Radioiodine Refractory DTC, Lenvatinib naive and able to provide written informed consent.
• Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) (including the follicular variants and other variants), Follicular thyroid cancer (FTC) (including Hurthle cell, Clear cell and Insular subtypes).
• Measurable disease meeting the following criteria: i) At least 1 lesion \>= 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 RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). ii) Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have shown evidence of PD based on RECIST 1.1 to be deemed a target lesion.
• Evidence of disease progression within 12 months of screening scan.
• Require thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than \[\<\] 4.0 milli-international units per liter \[mIU/L\]).
• Participant must be radioiodine-refractory or resistant within 12 months of radioiodine therapy and have 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 substantially increased in size within 12 months of radioiodine therapy, despite demonstration of radioiodine activity at the time of that treatment by pre- or post-treatment scanning.
• Cumulative activity of radioiodine of greater than (\>) 600 milliecurie (mCi) or 22 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Based on following laboratory assessment:
• Creatinine clearance \>= 30 milliliter per minute (mL/min) according to the Cockcroft and Gault formula.
• Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to (\<=) 1.5.
• Adequate bone marrow function:
• i. Absolute neutrophil count (ANC) \>=1.5\*10\^9/liter (L) ii. Hemoglobin \>= 9.0 gram per deciliter (g/dL) (can be corrected by growth factor or transfusion) iii. Platelet count \>=100 \* 10\^9/L

You may not qualify if:

• Anaplastic or medullary carcinoma of the thyroid.
• Two or more prior vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted therapies or any ongoing treatment for iodine-131 (131I) refractory DTC other than TSH-suppressive thyroid hormone therapy.
• Blood pressure (BP) \>= 140 millimeter of mercury (mmHg) Systolic and \>= 90 mmHg Diastolic at screening with or without antihypertensive medications.
• Woman who are lactating or pregnant at screening or baseline.
• Participants who received any anticancer treatment 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).
• Gastrointestinal malabsorption or any other condition that in the opinion of the investigator affected the absorption of Lenvatinib.
• Participant has history of congestive heart failure with New York Heart Association (NYHA) Classification \> II, unstable angina, myocardial infarction, serious cardiac arrhythmia, or stroke within the past 6 months.
• Electrocardiogram (ECG) with QT interval (QTc) interval \>= 450 millisecond (msec). (According to Bazett's formula).
• Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. (Treatment with low molecular weight heparin \[LMWH\] will be allowed).
• Existing anti-cancer therapy-related toxicities of CTCAE version 4.03 grade \>= 2, except alopecia and infertility.
• Any history of or concomitant medical condition that, in the opinion of the investigator, would compromise participant's ability to safely complete the protocol.
• Active infection (any infection requiring treatment).
• Active malignancy (except for differentiated thyroid carcinoma, 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.
• Epistaxis or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Known intolerance to Lenvatinib (or any of the excipients).

Sponsors & Collaborators

• Eisai Pharmaceuticals India Pvt. Ltd: lead

Study Sites (11)

Shetty's Hospital

Bangalore, Karnataka, 560068, India

Location

Regional Cancer Centre, RCC, Thiruvananthapuram

Thiruvananthapuram, Kerala, 695011, India

Location

Deenanath Mangeshkar Hospital

Pune, Maharashtra, 411004, India

Location

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Indraprastha Apollo Hospital

New Delhi, National Capital Territory of Delhi, 110076, India

Location

All India Institute of Medical Sciences

Bhubaneshwar, Odisa, 751019, India

Location

S. P. Medical College & A. G. Hospitals

Bikaner, Rajasthan, 334003, India

Location

Tata Memorial Hospital

Mumbai, 400012, India

Location

BL Kapoor Hospital, New Delhi

New Delhi, 110005, India

Location

Indrayani Hospital, Alandi

Pune, 412105, India

Location

City Cancer Centre

Vijayawada, 520002, India

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Medical Director

  Eisai Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: June 29, 2018
• Study Start: April 1, 2018
• Primary Completion: September 4, 2025
• Study Completion: September 4, 2025
• Last Updated: March 6, 2026

Record last verified: 2026-02

Locations

IN (11)