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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01321554
First received: March 10, 2011
Last updated: December 18, 2014
Last verified: November 2014
  Purpose
This is a multicenter, randomized, double-blind, Placebo-controlled Phase 3 study to compare the PFS of subjects with 131I-refractory DTC and radiographic evidence of disease progression within the prior 12 months, treated with E7080 (lenvatinib) 24 mg by continuous once daily (QD) oral dosing versus Placebo.

Condition Intervention Phase
Thyroid Cancer
Drug: lenvatinib 24 mg administered orally, once a day
Drug: Placebo 24 mg administered orally, once a day
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • To compare the Progression-free Survival (PFS) of subjects with 131IRefractory differentiated thyroid cancer (DTC) with radiographic evidence of disease progression within the prior 12 months treated with lenvatinib versus Placebo. [ Time Frame: Date of randomization to the date of disease progression (measured every 8 weeks) or death (whichever occurs first) as determined by blinded independent imaging review ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare Overall Response Rate (ORR) (Complete and Partial Responses, CR and PR) of subjects treated with lenvatinib versus Placebo. [ Time Frame: Date of randomization to the date of disease progression (measured every 8 weeks) or death ] [ Designated as safety issue: No ]

Enrollment: 392
Study Start Date: March 2011
Estimated Study Completion Date: March 2015
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lenvatinib Drug: lenvatinib 24 mg administered orally, once a day
Subjects with confirmation of disease progression by independent imaging review, while receiving blinded study drug may request to receive open label lenvatinib and enter the Optional Open Label lenvatinib Treatment Period of the Extension Phase. Subjects who request to receive open label lenvatinib(at the time of confirmed progression) will be informed whether they received placebo or lenvatinib during the period of blinded study drug administration. Subjects who received lenvatinib will not be eligible for the open-label phase.
Other Name: lenvatinb E7080
Experimental: Placebo Drug: Placebo 24 mg administered orally, once a day
Subjects with confirmation of disease progression by independent imaging review, while receiving blinded study drug may request to receive open label lenvatinib and enter the Optional Open Label lenvatinib Treatment Period of the Extension Phase. Subjects who request to receive open label lenvatinib ( at the time of confirmed progression) will be informed whether they received placebo or lenvatinib during the period of blinded study drug administration.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION

  1. Subjects must have histologically or cytologically confirmed diagnosis of one of the following differentiated thyroid cancer (DTC) subtypes:

    1. Papillary thyroid cancer (PTC) i. Follicular variant ii. Variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hurthle cell variant of papillary carcinoma, poorly differentiated)
    2. Follicular thyroid cancer (FTC) i. Hurthle cell ii. Clear cell iii. Insular
  2. Measurable disease meeting the following criteria and confirmed by central radiographic review:

    1. At least 1 lesion of greater than or equal to 1.0 cm in the longest diameter for a non-lymph node or greater than or equal to 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). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of greater than or equal to 1.5 cm
    2. Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
  3. Subjects must show evidence of disease progression within 12 months (an additional month will be allowed to accommodate actual dates of performance of screening scans, i.e., 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
  4. Subjects must be 131I-refractory / resistant as defined by at least one of the following:

    1. One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan
    2. One or more measurable lesions that has progressed by RECIST 1.1 within 12 months of 131I therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning. These subjects must not be eligible for possible curative surgery
    3. Cumulative activity of 131I of >600 mCi or 22 gigabequerels (GBq), with the last dose administered at least 6 months prior to study entry
  5. Subjects may have received 0 or 1 prior VEGF / VEGFR-targeted therapy ( for example sorafenib, sunitinib, pazopanib, etc.)
  6. Subjects 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 of steroids for one month
  7. Subjects must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than or equal to 5.50 mcu/mL). When tolerated by the subject, thyroxine dose should be changed to achieve TSH suppression (TSH less than 0.50 mcu/mL) and this dose can be changed concurrently upon starting lenvatinib
  8. All chemotherapy or radiation-related toxicities must have resolved to less than Grade 2 severity, except alopecia and infertility
  9. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 ? 2
  10. Adequately controlled blood pressure with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1
  11. Adequate renal function defined as calculated creatinine clearance less than or equal to 30 mL/min per the Cockcroft and Gault formula
  12. Adequate bone marrow function:

    1. Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 x 10^3/micro L)
    2. Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 x 10^9/L)
    3. Hemoglobin greater than or equal to 9.0 g/dL
  13. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5
  14. Adequate liver function:

    1. Bilirubin less than or equal to 1.5 x the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
    2. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (less than or equal to 5 x ULN if subject has liver metastases). If alkaline phosphatase is >3 x ULN (in absence of liver metastases) or >5 x ULN (in presence of liver metastases) AND the subject also is known to have bone metastases, the liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase
  15. Males or females age greater than or equal to 18 years at the time of informed consent
  16. All females must have a negative serum or urine pregnancy test. Females of childbearing potential and male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception
  17. Voluntary provision of written informed consent and the willingness and ability to comply with all aspects of the protocol

EXCLUSION

  1. Anaplastic or Medullary carcinoma of the thyroid
  2. Two or more prior VEGF / VEGFR-targeted therapies or any ongoing treatment for 131I-refractory DTC other than TSH-suppressive thyroid hormone therapy
  3. Prior treatment with lenvatinib (E7080)
  4. Subjects who have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. This does not apply to the use of TSH-suppressive thyroid hormone therapy
  5. Major surgery within 3 weeks prior to the first dose of study drug
  6. Subjects having >1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein greater than or equal to 1 g/24h will be ineligible
  7. Gastrointestinal malabsorption, or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib (E7080).
  8. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment
  9. Prolongation of QTc interval to >480 msec
  10. 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) is allowed)
  11. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
  12. Active infection (any infection requiring treatment)
  13. 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
  14. Known intolerance to any of the study drugs (or any of the excipients)
  15. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
  16. Females who are pregnant or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01321554

  Hide Study Locations
Locations
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
La Jolla, California, United States
Los Gatos, California, United States
Orange, California, United States
Torrence, California, United States
United States, Colorado
Aurora, Colorado, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Orlando, Florida, United States
Weston, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Kentucky
Lexington, Kentucky, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Lansing, Michigan, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New Hampshire
Lebanon, New Hampshire, United States
United States, New Jersey
Neptune, New Jersey, United States
United States, New York
Bronx, New York, United States
United States, Ohio
Columbus, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
United States, Washington
Seattle, Washington, United States
Australia, New South Wales
St Leonards, New South Wales, Australia
Australia, Queensland
Herston, Queensland, Australia
Australia, Tasmania
Hobart, Tasmania, Australia
Australia, Victoria
Melbourne, Victoria, Australia
Australia
Heidelberg, Australia
Austria
Wien, Austria
Belgium
Bruxelles, Belgium
Edegem, Belgium
Namur, Belgium
Brazil
Brasilia - DF, Brazil
Salvador/BA, Brazil
Sao Paulo - SP, Brazil
Sao Paulo, Sao Paulo, Brazil
Canada, Ontario
London, Ontario, Canada
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Canada
Quebec, Canada
Chile
Santiago, Chile
Temuco, Chile
Vina del Mar, Chile
Denmark
Odense, Denmark
France
Angers, France
Bordeaux, France
Caen, France
Clermont-Ferrand, France
Dijon, France
Lyon, France
Marseille, France
Nice, France
Paris, France
Strasbourg, France
Villejuif, France
Germany
Essen, Germany
Hannover, Germany
Leipzig, Germany
Minz, Germany
Tubingen, Germany
Wurzburg, Germany
Italy
Catania, Italy
Livorno, Italy
Milano, Italy
Monserrato, Italy
Napoli, Italy
Padova, Italy
Pisa, Italy
Roma, Italy
Rozzano, Italy
Torino, Italy
Viagrande, Italy
Japan
Nagoya, Aichi, Japan
Kashiwa, Chiba, Japan
Fukui-city, Fukui, Japan
Kobe-city, Hyogo, Japan
Koto-ku, Tokyo, Japan
Korea, Republic of
Daejeon, Korea, Republic of
Gyeonggi-do, Korea, Republic of
Seoul, Korea, Republic of
Poland
Gliwice, Poland
Kielce, Poland
Poznan, Poland
Portugal
Lisboa, Portugal
Porto, Portugal
Romania
Bucharest, Romania
Cluj-Napoca, Romania
Russian Federation
Obninsk, Russian Federation
Ufa, Russian Federation
Spain
Malaga, Andalucia, Spain
Barcelona, Cataluna, Spain
Barcelona, Spain
Madrid, Spain
Sweden
Goteborg, Sweden
Lund, Sweden
Thailand
Bangkok, Thailand
Chiangmai, Thailand
Pathumwan, Thailand
United Kingdom
Aberdeen, United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Sheffield, United Kingdom
Sutton, United Kingdom
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Eisa Inc Eisai Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01321554     History of Changes
Other Study ID Numbers: E7080-G000-303 
Study First Received: March 10, 2011
Last Updated: December 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2016