Anaplastic Thyroid Cancer (ATC) MedDRA version: 20.0 Level: PT Classification code 10002240 Term: Anaplastic thyroid cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: LENVIMA
Product Name: Lenvatinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lenvatinib
CAS Number: 417716-92-8
Current Sponsor code: E7080
Other descriptive name: Lenvatinib
C
Sponsors
EISAI LIMITED
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females age = 18 years at the time of informed consent form (ICF). 2. Subjects must have histological diagnosis consistent of ATC. Cytologic diagnosis by fine needle aspiration alone is not sufficient. Histologic diagnosis may be made by core needle biopsy, incisional biopsy, thyroidectomy, or other surgical biopsy. Fresh tumor biopsies (re-biopsy) should be obtained whenever feasible. The central pathology review may take place prior to or after the subject starts treatment with lenvatinib. a. Central review of pathology is required for study participation, but not required prior to enrollment or start of treatment in order to avoid delay. If the results of central pathology review are not available prior to the start of study treatment, the confirmation of diagnosis of ATC at the local laboratory is mandatory prior to scheduled start of treatment with lenvatinib. b. If central pathology review indicates a diagnosis other than ATC, the subject may continue treatment with lenvatinib per standard of care, at the discretion of the treating investigator. Subjects deemed to have another diagnosis (not ATC) will be taken off this study and replaced for the purpose of efficacy analyses. c. Differentiated thyroid carcinoma (DTC) with focus loci of ATC is allowed. If a subject has pathology showing a small focus of ATC arising out of DTC and the measurable disease is not fully consistent with ATC, confirmation of ATC by biopsy is required. d. An incidental focus of medullary thyroid cancer (MTC), DTC, and/or poorly differentiated thyroid cancer in a subject with ATC is allowed. e. Histological diagnosis of ATC made through surgical resection is also acceptable. 3. Prior neoadjuvant, adjuvant or palliative chemotherapy for ATC is allowed. 4. Measurable disease based on investigator’s assessments meeting the following criteria: a. At least 1 lesion of = 10 mm in the longest diameter for a non-lymph node or = 15 mm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography (CT) or magnetic resonance imaging (MRI). b. Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency ablation must show evidence of subsequent progressive disease (substantial size increase of = 20%) to be deemed a target lesion. 5. Subjects 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 steroids for 1 month prior to enrollment. 6. All previous chemotherapy or radiation therapy-related toxicities, except dry mouth, dysphagia, esophagitis, mucositis, alopecia, and irreversible late sequelae of radiation therapy, must have resolved to Grade 0 or 1 per Common Terminology Criteria for Adverse Events (CTCAE v 4.03), and all wounds from prior surgery must have adequately recovered. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 8. Blood pressure (BP) = 140/90 mmHg at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1. 9. Adequate renal function as evidenced by calculated creatinine clearance = 30 mL/min according to the Cockcroft and Gault formula. 10. Adequate bone marrow function: a. Absolute neutrophil count (ANC) = 1.5 x 109/L and b. Hemoglobin = 9.0 g/dL (can be corrected by growth fac
Exclusion criteria
Exclusion criteria: 1. Differentiated thyroid cancer (DTC) or MTC. However, ATC arising out of DTC is allowed, as long as the measurable disease is clinically consistent with ATC ie, rapidly progressive and/or 18F fluorodeoxyglucose (FDG)-avid. 2. Newly diagnosed patients who are considered appropriate candidates for comprehensive multimodality treatment (involving surgery and/or external beam radiotherapy or chemo radiotherapy). 3. Prior treatment with lenvatinib or any tyrosine kinase inhibitor (except for combination therapy of radiation and reduced dose of TKI given for the purpose of radiosensitization). 4. Major surgery within 2 weeks prior to the first dose of lenvatinib. 5. Any anti-cancer treatment within 14 days or any investigational agent within 30 days before the first dose of study drug. 6. Radiotherapy within 3 weeks prior to the first dose of lenvatinib. 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 hours will be ineligible. 8. Significant cardiovascular impairment: History of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II, (b) unstable angina, (c) myocardial infarction, (d) stroke, or (e) cardiac arrhythmia associated with impairment within 6 months of the first dose of study drug. 9. A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval >500 msec). 10. Active infection requiring systemic therapy. 11. Clinically significant hemoptysis or tumor bleeding within two weeks prior to first dose of lenvatinib 12. Radiographic evidence of major blood vessel invasion/infiltration. 13. Other active malignancy (except definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within past 24 months. 14. Scheduled for major surgery during the study. 15. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 16. Females of childbearing potential who: •? Do not agree to use a highly effective method of contraception (eg, total abstinence [if it is their preferred and usual lifestyle], an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) within 30 days before study entry and throughout the entire study period or for 30 days after study drug discontinuation. •?Are currently totally abstinent (as their preferred and usual lifestyle), and who do not agree to be totally abstinent during the study period or for 30 days after study drug discontinuation. •?Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 30 days after study drug discontinuation. • Are using oral hormonal contraceptives and who do not agree to add a barrier method. •?(NOTE: All
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate ORR (CR and PR) by investigator review in subjects with ATC treated with lenvatinib.;Secondary Objective: - To evaluate 12-week PFS - To evaluate 6-month OS - To evaluate median PFS and median OS - To evaluate safety and tolerability of lenvatinib in subjects with ATC;Primary end point(s): The primary efficacy endpoint is ORR as determined by investigator review, using RECIST 1.1. ORR is the proportion of subjects who have best overall response (BOR) of CR or PR.;Timepoint(s) of evaluation of this end point: Timepoint will be approximately 6 months following the enrollment of the last subject (Section 9.7.1.6.4) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are: ? - To evaluate 12-week PFS ?- To evaluate 6-month OS ?- To evaluate median PFS and median OS ?- To evaluate safety and tolerability of lenvatinib in subjects with ATC ;Timepoint(s) of evaluation of this end point: Timepoint will be approximately 6 months following the enrollment of the last subject (Section 9.7.1.6.4) | — |
Countries
Australia, France, Italy, Poland, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Europe Ltd
Outcome results
None listed