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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02657369




Registration number
NCT02657369
Ethics application status
Date submitted
13/01/2016
Date registered
15/01/2016

Titles & IDs
Public title
A Phase 2 Trial of Lenvatinib for the Treatment of Anaplastic Thyroid Cancer (ATC)
Scientific title
An Open-Label, Single-Arm, Multicenter, Phase 2 Trial of Lenvatinib for the Treatment of Anaplastic Thyroid Cancer (ATC)
Secondary ID [1] 0 0
2015-001929-17
Secondary ID [2] 0 0
E7080-M000-213
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thyroid Carcinoma, Anaplastic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Lenvatinib - Participants will receive lenvatinib 24 milligrams (mg) (2 10-mg capsules and one 4-mg capsule) once daily by oral administration at approximately the same time each morning for up to approximately 24 months.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From the date of beginning of lenvatinib administration to the date of first documentation of disease progression or death, whichever occurred first (up to Month 27)
Secondary outcome [1] 0 0
Progression-free Survival (PFS) Rate
Timepoint [1] 0 0
From the date of beginning of lenvatinib administration up to the date of first documentation of confirmed disease progression or death, whichever occurred first (up to Week 12)
Secondary outcome [2] 0 0
Overall Survival (OS) Rate
Timepoint [2] 0 0
From the date of beginning of lenvatinib administration up to date of death from any cause (up to Month 6)
Secondary outcome [3] 0 0
Median PFS
Timepoint [3] 0 0
From the date of beginning of lenvatinib administration to the date of first documentation of confirmed disease progression or death, whichever occurred first (up to Month 27)
Secondary outcome [4] 0 0
Median OS
Timepoint [4] 0 0
From the date of beginning of lenvatinib administration up to date of death from any cause (up to Month 27)

Eligibility
Key inclusion criteria
1. Participants must have histological diagnosis consistent of Anaplastic Thyroid Cancer (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 participant starts treatment with lenvatinib.

1. 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.
2. If central pathology review indicates a diagnosis other than ATC, the participant may continue treatment with lenvatinib per standard of care, at the discretion of the treating investigator. Participants deemed to have another diagnosis (not ATC) will be taken off this study and replaced for the purpose of efficacy analyses.
3. Differentiated thyroid carcinoma (DTC) with focus loci of ATC is allowed. If a participant 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.
4. An incidental focus of medullary thyroid cancer (MTC), DTC, and/or poorly differentiated thyroid cancer in a participant with ATC is allowed.
5. Histological diagnosis of ATC made through surgical resection is also acceptable.
2. Prior neoadjuvant, adjuvant, or palliative chemotherapy for ATC is allowed.
3. Measurable disease based on investigator's assessments meeting the following criteria:

1. At least 1 lesion of = 10 millimeters (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 Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 using computerized tomography (CT) or magnetic resonance imaging (MRI).
2. 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.
4. Participants 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.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. Blood pressure (BP) = 140/90 millimeter of mercury (mmHg) at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1.
8. Adequate renal function as evidenced by calculated creatinine clearance = 30 milliliter/ minute (mL/min) according to the Cockcroft and Gault formula.
9. Adequate bone marrow function:

1. Absolute neutrophil count (ANC) = 1.5 x 10^9/liter (L) and
2. Hemoglobin = 9.0 grams/deciliter (g/dL) (can be corrected by growth factor or transfusion) and
3. Platelet count = 100 x 10^9/L.
10. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) = 1.5.
11. Adequate liver function:

1. Bilirubin = 1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome;
2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 3 x ULN (= 5 x ULN if participant has liver metastases). If ALP is > 3 x ULN (in the absence of liver metastases) or > 5 x ULN (in the presence of liver metastases) AND participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.
12. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 i.e., rapidly progressive and/or 18F fluorodeoxyglucose (FDG)-avid.
2. Newly diagnosed participants 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 (TKI) - (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. Participants having > 1 + proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria. Participants with urine protein = 1 gram/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 (e.g., a repeated demonstration of a QTc interval >500 milliseconds (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 international units/liter (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:

1. Do not agree to use a highly effective method of contraception (ie, total abstinence, [if it is their preferred and usual lifestyle], an intrauterine device or intrauterine system, 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 and for 30 days after study drug discontinuation.
2. Are currently totally abstinent (as their preferred and usual lifestyle), and who do not agree to be totally abstinent during the study period and for 30 days after study drug discontinuation.
3. 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 and for 30 days after study drug discontinuation.
4. Are using oral hormonal contraceptives and who do not agree to add a barrier method.

(NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [i.e. bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing]).

For sites outside of the European Union (EU), it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, i.e. double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.
17. Evidence of clinically significant disease (e.g., cardiovascular, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
18. Known intolerance to the study drug or any of the excipients.
19. Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/09/2018
Sample size
Target
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- St Leonards
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
- St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
France
State/province [12] 0 0
Calvados
Country [13] 0 0
France
State/province [13] 0 0
Gironde
Country [14] 0 0
France
State/province [14] 0 0
Maine Et Loire
Country [15] 0 0
France
State/province [15] 0 0
Rhone
Country [16] 0 0
France
State/province [16] 0 0
Val De Marne
Country [17] 0 0
Italy
State/province [17] 0 0
Milano
Country [18] 0 0
Italy
State/province [18] 0 0
Pisa
Country [19] 0 0
Italy
State/province [19] 0 0
Roma
Country [20] 0 0
Italy
State/province [20] 0 0
Siena
Country [21] 0 0
United Kingdom
State/province [21] 0 0
South Glamorgan
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Strathclyde
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Eisai IPD sharing statement: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02657369