A phase 3 trial studying how well E7080 works in treating patients with advanced thyroid cancer who no longer gain benefit from radioactive iodine therapy. The trial is taking place worldwide, patients and their physician do not know if they are receiving the active drug or a dummy drug.
- Conditions
- 131I-refractory differentiated thyroid cancer (DTC)MedDRA version: 14.0 Level: PT Classification code 10055107 Term: Thyroid cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-023783-41-ES
- Lead Sponsor
- Eisai Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 360
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 >or= 1.0 cm in the longest diameter for a non-lymph node or >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 >or= 1.5 cm
b. Lesions that have had EBRT or loco-regional 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 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:
a. One or more measurable lesions that do not demonstrate 131I 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
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 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit
11. Adequate renal function defined as calculated creatinine clearance >or= 30 mL/min per the Cockcroft and Gault formula
12. Adequate bone marrow function: a. ANC >or= 1500/mm3 b. Platelets >or= 100,000/mm3 c. Hemoglobin >or= 9.0 g/dL
13. Adequate blood coagulation
1. Anaplastic or Medullary carcinoma of the thyroid
2. Two or more prior VEGF / VEGFR-targeted therapies or any ongoing treatment for 131Irefractory 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 >or= 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method