131I-refractory differentiated thyroid cancer (DTC) MedDRA version: 20.0 Level: PT Classification code 10055107 Term: Thyroid cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Subjects must have histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: a 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, Hürthle cell variant of papillary carcinoma, poorly differentiated) b FTC i Hürthle cell ii Clear cell iii 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 which is serially measurable according to RECIST 1.1 using CT/MRI. If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of = 1.5 cm. b Lesions that have had EBRT or locoregional therapies such as 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 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 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. 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 may have received 0 or 1 prior VEGF/VEGFR-targeted therapy. Each of the VEGF/VEGFR targeted agents will be counted individually. 6 Patients 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 TSH should not be elevated. When tolerated by the subject, thyroxine dose should be changed to achieve TSH suppression and this dose can be changed concurrently upon starting E7080. 8. All chemotherapy or radiation-related toxicities must have resolved to < Grade 2 severity, except alopecia and infertility. 9. Subjects must have an ECOG Performance Status of 0–2. 10. Adequately controlled blood pressure with or without antihypertensive medications, defined as BP = 150/90 mm Hg 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 = 30 mL/min per the Cockcroft and Gault formula. 12. Adequate bone marrow function: a. ANC = 1500/mm3 b. Platelets = 100,000/mm3 c. Hemoglobin = 9.0 g/dL 13. Adequate blood coagulation function as evidenced by an INR = 1.5 14. Adequate liver function: a. Bilirubin = 1.5 × ULN except for unconjugated hyperbilirubinemia or Gilbert’s syndrome b. Alkaline phosphatase, ALT and AST = 3 × the ULN. 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 access the liver function instead of total alkaline phosphatase 15. Males or fe
Exclusion criteria
Exclusion criteria: 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 E7080 4. Subjects who have received any anticancer 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 anticancer 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 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein = 1 g/24 h will be ineligible. 7. Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of 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 ms 10. Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents requiring therapeutic 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 DTC or definitively treated melanoma insitu, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 E7080 versus placebo;Secondary Objective: To compare overall response rate (ORR) (complete and partial responses, CR and PR) of subjects treated with E7080 versus placebo • To compare overall survival of subjects treated with E7080 versus placebo • To compare safety and tolerability of E7080 versus placebo • To assess the pharmacokinetic (PK) profile of E7080 in subjects with DTC.;Primary end point(s): The primary endpoint for all subjects will be progression free survival (PFS);Timepoint(s) of evaluation of this end point: The primary analysis of PFS will be performed when approximately 214 progression events or deaths without disease progression have occurred in the study population, which is estimated to be approximately after the first subject is randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are overall response rate as determined by blinded IIR using RECIST 1.1 and overall survival. Exploratory Efficacy Endpoints are disease control rate (DCR), clinical benefit rate (CBR), and durable stable disease (SD) rate (duration of SD = 23 weeks).;Timepoint(s) of evaluation of this end point: ORR: CT/MRI neck/chest/abdomen/pelvis and other areas of known disease or newly suspected disease: at screening, every 8 weeks (Randomization Phase) once every 12 weeks and no less frequently than once every 24 weeks (Extension Phase); bone scan every 24 weeks. CT/MRI brain at screening and, if negative, to be repeated if clinically indicated, and within 1 week after a subject achieves a CR. For subjects with a history of treated brain metastases, brain scans at screening and every 8 weeks OS: every 4 weeks PK: predose, 0.5-4 hours, and 6-10 hours postdose on C1D1 and C1D15, and predose and 2-12 hours postdose on C2D1. Subsequently, predose only on Day 1 of Cycles 3, 4, 5, and 6. AEs/SAEs: throughout the study. AEs and concomitant meds collected 30 days from last dose. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Thailand, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Ltd
Outcome results
None listed