131I-refractory differentiated thyroid cancer (DTC) MedDRA version: 18.1 Level: PT Classification code 10066474 Term: Thyroid cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: LENVIMA
Product Name: lenvatinib
Product Code: E7080
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lenvatinib
CAS Number: 417716-92-8
Current Sponsor code: E7080
Other descriptiv
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must have histologically confirmed diagnosis of one of the following differentiated thyroid cancersubtypes: a. Papillary thyroid cancer ? 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) b. Follicular thyroid cancer ? Hürthle cell ? Clear cell ? Insular 2.Measurable disease meeting the following criteria and confirmed by central radiographic review: a. At least 1 lesion of =1.0 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 RECIST 1.1 using 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. b. Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency 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, ie, within =13 months) prior to signing informed consent, according to RECIST 1.1 assessed and confirmed by central radiographic review of CT and/or MRI. 4.Subjects must be 131I-refractory/resistant as defined by at least one of the following: a.One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan. b.One or more measurable lesions that have progressed according to RECIST 1.1 within 12 months after 131I therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or posttreatment scanning. These subjects must not be eligible for possible curative surgery. c. Cumulative activity of 131I of >600 mCi or 22 GBq, with the last dose administered at least 6 months prior to study entry. 5.Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, if they have remained clinically stable, asymptomatic, and off steroids for one month. 6.Subjects must be receiving thyroxine suppression therapy and TSH should not be elevated (TSH should be =5.50 mCi/mL).When tolerated by the subject, thyroxine dose should be changed to achieve TSH suppression. 7.All chemotherapy- or radiation-related toxicities must have resolved to Grade 3 × ULN (in absence of liver metastases) or >
Exclusion criteria
Exclusion criteria: 1. Anaplastic or medullary carcinoma of the thyroid. 2. Diagnosed with meningeal carcinomatosis. 3. Two or more prior VEGF/VEGFR-targeted therapies or any ongoing treatment for RR-DTC other than TSH-suppressive thyroid hormone therapy. 4. Prior treatment with lenvatinib. 5. Subjects 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 TSHsuppressive thyroid hormone therapy. 6. Major surgery within 3 weeks prior to randomization or elective surgery scheduled to performed during the study. 7. Subjects having >1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein =1 g/24 h will be ineligible. 8. Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of study drug. 9. 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. 10. 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 (eg, a repeated demonstration of a QTc interval >500 ms). 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 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. 14. Known intolerance to study drug (or any of the excipients). 15. Any medical or other condition that in the opinion of the investigator(s) would preclude the subject’s participation in a clinical study. 16. Females who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether a starting dose of lenvatinib 20 mg or 14 mg once daily (QD) will provide comparable efficacy (based on ORR6M) with an improved safety profile compared to 24 mg QD (based on treatment-emergent adverse events [TEAEs] of Grade 3 or higher in the first 6 months after randomization).;Secondary Objective: To evaluate PFS in subjects treated with lenvatinib doses of 24 mg, 20 mg, and 14 mg QD. To evaluate the PFS after next line of treatment (PFS2) in subjects treated with lenvatinib doses of 24 mg, 20 mg, and 14 mg QD. To evaluate the safety and tolerability of lenvatinib doses of 24 mg, 20 mg, and 14 mg QD. To evaluate the pharmacokinetic (PK)/pharmacodynamic relationship between exposure and biomarkers/efficacy/safety. To evaluate the impact of lenvatinib treatment on Health-Related Quality of Life (HRQoL) as measured by the instruments EQ-5D-3L and FACT-G.;Primary end point(s): ORR6M as assessed by investigator using RECIST 1.1. ORR6M is defined as the proportion of subjects with BOR of CR or PR at the Week 24 time point or earlier. Rate of TEAE with CTCAE grades of 3 or higher within 6 months after randomization (as of the Week 24 time point).;Timepoint(s) of evaluation of this end point: ORR6M as assessed by investigator using RECIST 1.1. Rate of TEAE with CTCAE grades of 3 or higher within 6 months after randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS, defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurs first. PFS censoring rules will be defined in the SAP and will follow FDA guidance. PFS2, defined as the time from randomization to second objective disease progression, or death from any cause, whichever occurs first. Overall safety profile and tolerability. Time to treatment discontinuation due to an AE. Number of dose reductions. Time to first dose reduction. Plasma PK lenvatinib exposure parameters. Inter-relationships of lenvatinib exposure, changes in thyroglobulin and/or TSH, other exploratory serum biomarkers, and changes in tumor burden and PFS. Relationship of lenvatinib exposure and changes in BP, and AEs of weight loss, fatigue, nausea, vomiting, diarrhea, and proteinuria CTCAE grades derived from urine protein measurements. Impact of lenvatinib treatment on HRQoL as assessed using the validated instruments EQ-5D-3L and FACT-G.;Timepoint(s) of evaluation of this end point: lPFS, PFS2, overall safety and tolerability | — |
Countries
Argentina, Australia, Belgium, Brazil, Denmark, France, Germany, Israel, Italy, Poland, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Limited
Outcome results
None listed