Overview

This trial is active, not recruiting.

Condition thyroid cancer
Treatments lenvatinib 24 mg administered orally, once a day, placebo 24 mg administered orally, once a day
Phase phase 3
Sponsor Eisai Inc.
Start date March 2011
End date November 2013
Trial size 392 participants
Trial identifier NCT01321554, E7080-G000-303

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
lenvatinib 24 mg administered orally, once a day lenvatinb E7080
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.
(Experimental)
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.

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by Eisai Inc..