Evaluating the Safety and Efficacy of Oral Lenvatinib in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology

NCT00784303 | Completed Phase 2 Results DMC

• 1 other identifier: E7080-G000-201
• Study Type: interventional
• Target: 117
• Locations: 6 countries
• Sites: 42

Brief Summary

The purpose of this study is to determine the safety and efficacy of oral lenvatinib in participants with medullary thyroid cancer (MTC) or radioiodine (131 I)-refractory/resistant differentiated thyroid cancer (DTC), unresectable differentiated thyroid cancers, stratified by Histology.

Conditions

Thyroid Cancer

Keywords

Thyroid Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  ORR was the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 for target lesions using magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent imaging review (IIR). CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper and Pearson.

  From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months

• Plasma Pharmacokinetics (PK): Steady State Area Under the Plasma Concentration Curve (AUC)

  Up to 9 samples per participant were obtained at specific time points. Plasma concentrations of lenvatinib were analyzed using standard analysis methods. Due to the sparse PK sampling in this study, the data were pooled with data from other Phase 1 studies conducted in participants with solid tumors for PK model development and covariate analysis. Individual exposure (steady state AUC) to lenvatinib in MTC and DTC subjects in this study was derived based on the individual predicted steady state AUC from the final PK model. Only data for participants taking 24 mg lenvatinib daily were reported (participants taking 20 mg lenvatinib daily were not included in this data set).

  Cycle 1 Day 1 (predose and at 0.5 and 2 hours postdose), Cycle 1 Day 8 (predose), Cycle 2 Day 1 (predose and at 0.5 and 2 hours postdose), and Cycle 3 Day 1 (predose and at 2 hours postdose) (Cycle length= 28 days)

Secondary Outcomes (15)

• Change From Baseline in Free Thyroxine (T4)

  Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)

• Change From Baseline in Free Thyroid Stimulating Hormone (TSH)

  Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)

• Percent Change From Baseline in Concentrations of Thyroglobulin (DTC Only)

  Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 19, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)

• Percent Change From Baseline in Concentrations of Calcitonin (MTC Only)

  Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)

• Percent Change From Baseline in Concentrations of Carcinoembryonic Antigen (CEA) (MTC Only)

  Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)

Study Arms (2)

DTC cohort

EXPERIMENTAL

This arm will enroll participants with radioiodine (131 I)-refractory/resistant differentiated thyroid cancer.

Drug: Lenvatinib (DTC Cohort)

MTC cohort

EXPERIMENTAL

This arm will enroll participants with medullary thyroid cancer.

Drug: Lenvatinib (MTC Cohort)

Interventions

Lenvatinib (DTC Cohort) DRUG

24 mg lenvatinib (two 10 mg tablets and one 4 mg tablet) given orally, once daily, or 10 mg lenvatinib orally twice daily (20 mg total). Out of 58 participants in the DTC cohort, 56 participants received 24 mg lenvatinib once daily and 2 participants received 10 mg lenvatinib twice daily (total 20 mg daily), given continuously in 28-day treatment cycles.

Also known as: E7080, LENVIMA

DTC cohort

Lenvatinib (MTC Cohort) DRUG

24 mg lenvatinib (two 10 mg tablets and one 4 mg tablet) given orally, once daily given continuously in 28-day treatment cycles.

Also known as: E7080, LENVIMA

MTC cohort

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC) or differentiated thyroid cancer (DTC).
• Measurable disease meeting the following criterion:
• At least one lesion (greater than or equal to 1.5 cm in longest diameter for non-lymph nodes and greater than or equal to 2.0 cm in longest diameter for lymph nodes) which is serially and accurately measurable according to modified response evaluation criteria in solid tumours (RECIST) using either computed tomography (CT) or magnetic resonance imaging (MRI).
• Lesions that have had electron beam radiotherapy must show evidence of progressive disease based on modified RECIST to be deemed a target lesion.
• Evidence of disease progression by RECIST using site assessment of CT/MRI scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry.
• DTC must be 131-I refractory/resistant: never demonstrated 131-I uptake, progression despite 131-I uptake, or cumulative dose of 131-I of greater than 600 millicurie (mCi) (last dose given at least 6 months prior to study entry).
• Well controlled blood pressure prior to study entry.

You may not qualify if:

• Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid.
• Brain or leptomeningeal metastases.
• Significant cardiovascular impairment (history of congestive heart failure, New York Heart Association \[NYHA\] Class II, unstable angina or myocardial infarction within 6 months of study start, or serious cardiac arrhythmia).
• Marked baseline prolongation of QT/corrected QT (QTc) interval.
• Proteinuria greater than 1+ or greater than 30 mg in dipstick testing.
• Active hemoptysis (bright red blood of at least one-half teaspoon) in the 28 days prior to study entry.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (42)

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Little Rock, Arkansas, United States

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Los Angeles, California, United States

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Los Gatos, California, United States

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Mission Viejo, California, United States

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Santa Monica, California, United States

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Torrance, California, United States

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Aurora, Colorado, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Roswell, Georgia, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Boston, Massachusetts, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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Jefferson City, Missouri, United States

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Lebanon, New Hampshire, United States

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Montclair, New Jersey, United States

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Houston, Texas, United States

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Long Beach, Washington, United States

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Seattle, Washington, United States

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Madison, Wisconsin, United States

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St Leonards, New South Wales, Australia

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Brisbane, Australia

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Melbourne, Australia

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Lyon, France

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Paris, France

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Reims, France

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Villejuif, France

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Ferrara, Italy

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Milan, Italy

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Naples, Italy

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Pisa, Italy

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Rome, Italy

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Siena, Italy

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Gliwice, Poland

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Poznan, Poland

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Cardiff, United Kingdom

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Glasgow, United Kingdom

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London, United Kingdom

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Sutton, United Kingdom

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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

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2008
• First Posted: November 3, 2008
• Study Start: November 6, 2008
• Primary Completion: April 11, 2011
• Study Completion: March 29, 2019
• Last Updated: April 22, 2020
• Results First Posted: August 1, 2019

Record last verified: 2019-03

Locations

FR (4); AU (3); IT (6); PL (2); US (23); GB (4)