131-I-Refractory Differentiated Thyroid Cancer
Conditions
Sponsors
Eisai Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Subjects must have histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: (1)Papillary thyroid cancer (PTC) * 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, Hurthle cell variant of papillary carcinoma, poorly differentiated) (2)Follicular thyroid cancer (FTC) * Hurthle cell * Clear cell * Insular 2. Measurable disease meeting the following criteria and confirmed by central radiographic review: * 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 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 >- 1.5 cm * 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 scans, i.e., within - 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. 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 thyroid stimulating hormone (TSH) should not be elevated (TSH should be -- 30 mL/min per the Cockcroft and Gault formula (Appendix 4) 12. Adequate bone marrow function: * Absolute neutrophil count (ANC) >- 1500/mm3 (>- 1.5 x 103/microliter) * Platelets >- 100,000/mm3 (>- 100 x 109/L) * Hemoglobin >- 9.0 g/dL 13. Ade
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from this study: 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 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 >- 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 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 QTcF 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free-Survival 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. [ 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 ] | — |
Outcome results
None listed