A Phase 2 trial to determine if there is a lower starting dose of lenvatinib (20mg or 14mg daily) that will cause fewer side effects and work as well as a 24mg starting dose in treating adults with thyroid cancer, who are not responding to treatment, or whose cancer has reappeared following an initial recovery.
- Conditions
- 131I-refractory differentiated thyroid cancer (DTC)MedDRA version: 18.1Level: PTClassification code 10066474Term: Thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005199-27-SE
- Lead Sponsor
- Eisai Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
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 <2 severity per CTCAE v4.03, except alopecia and infertility.
8. Subjects must have an ECOG Performance Status of 0, 1 or 2.
9.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 Cycle 1/Day 1.
10. Adequate renal function defined as calculated creatinine clearance =30 mL/min per the Cockcroft and Gault formula.
11.Adequate bone marrow function: a. Absolute neutrophil count =1500/mm3 b. Platelets =100,000/mm3 c. Hemoglobin =9.0 g/dL
12. Adequate blood coagulation function INR =1.5.
13.Adequate liver function:
a. Bilirubin =1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert’s syndrome.
b. Alkaline phosphatase, ALT, and AS =3 × ULN (=5 × ULN if subject has liver metastases). If alkaline phosphatase is >3 × ULN (in absence of liver metastases) or >5 × ULN (in presence
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.
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