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Differentiated Thyroid Cancer (DTC)Phase 3NCT02966093

A Trial of Lenvatinib (E7080) in Radioiodine (131 I)-Refractory Differentiated Thyroid Cancer in China

A Phase 3 study testing Lenvatinib in people with Differentiated Thyroid Cancer (DTC), run by Eisai Co., Ltd. at 24 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary purpose of this study is to compare the progression-free survival (PFS) of participants with radioiodine (131 I)-refractory differentiated thyroid cancer (DTC) and radiographic evidence of disease progression within the prior 12 months treated with lenvatinib 24 mg by continuous once daily (QD) oral dosing… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Differentiated Thyroid Cancer (DTC)
What is being tested?
Lenvatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
151 participants
Where
24 sitesChina
Study dates
11 Jan 2017to 29 Dec 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically or cytologically confirmed diagnosis of one of the following Differentiated Thyroid Cancer (DTC) subtypes:
  • Papillary thyroid cancer (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. Follicular thyroid cancer (FTC) i. Hürthle cell ii. Clear cell iii. Insular
  • Measurable disease meeting the following criteria and confirmed by central radiographic review:
  • At least 1 lesion of ≥ 1.0 centimeter (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 Response Evaluation Criteria in Solid Tumors (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 locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease (substantial size increase of ≥ 20%) to be deemed a target lesion.
  • Participants must show evidence of disease progression comparing (a) scan in screening and (b) historical scan obtained 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.
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  • Participants must not be eligible for possible curative surgery and must be radioiodine (131 I)- refractory / resistant as defined by at least one of the following:
  • One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan
  • One or more measurable lesions that has progressed by RECIST 1.1 within 12 months of 131 I therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning.
  • Cumulative activity of 131 I of > 600 millicurie (mCi) or 22 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry
  • Participants may have received 0 or 1 prior vascular endothelial growth factor/ vascular endothelial growth factor receptor (VEGF/VEGFR)-targeted therapy (for example sorafenib, sunitinib, pazopanib, etc.). Each of the VEGF/VEGFR targeted agents will be counted individually, regardless of the duration of its administration.
  • 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 of steroids for one month.
  • Participants must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should be ≤ 0.1 milliunits/Liter (mU/L) (≤ 0.5 mU/L if there is safety concern).
  • All chemotherapy or radiation related toxicities must have resolved to < Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE v 4.0), except alopecia and infertility.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 millimeter of mercury (mm Hg) at screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1
  • Adequate renal function defined as calculated creatinine clearance
  • ≥ 30 mL/min per the Cockcroft and Gault formula
  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) ≥ 1500 per cubic meter (mm3) (≥ 1.5 × 10^3/micro liter [μL])
  • Platelets ≥ 100,000/mm3 (≥ 100 × 10^9/ liter [L])
  • Hemoglobin ≥ 9.0 gram per deciliter (g/dL)
  • Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤ 1.5
  • Adequate liver function:
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
  • Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN if participant has liver metastases).
  • Males or females age ≥ 18 years at the time of informed consent
  • Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 international unit per liter (IU/L) or equivalent units of 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.
  • 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 (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
  • Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, 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) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
  • Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). Those with partners using hormonal contraceptives must also be using an additional approved method of contraception, as described previously.
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Who cannot join

  • Anaplastic or medullary carcinoma of the thyroid
  • Two or more prior VEGF/VEGFR-targeted therapies or any ongoing treatment for 131 I-refractory DTC other than TSH-suppressive thyroid hormone therapy
  • Prior treatment with lenvatinib
  • Participants who have received any anticancer treatment (including Chinese herbal medicine specified for the treatment of tumor) within 21 days or any investigational agent within 30 days prior to the first dose of study drug. This does not apply to the use of TSH-suppressive thyroid hormone therapy.
  • Major surgery within 3 weeks prior to the first dose of study drug
  • Participants having > 1 + proteinuria on urine dipstick testing (Participants with urine protein < 1 g/24 hour (h) will be eligible).
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  • Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib
  • 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
  • Prolongation of corrected Q wave and T wave (QTc) interval to > 480 millisecond (ms)
  • Bleeding or thrombotic disorders (Treatment with low molecular weight heparin [LMWH] is allowed.)
  • Radiographic evidence of major blood vessel invasion/infiltration
  • Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
  • Active infection (any infection requiring systemic treatment)
  • Active malignancy (except for DTC or definitively treated basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months
  • Known intolerance to any of the study drugs (or any of the excipients)
  • Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
  • Females who are pregnant or breastfeeding

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

China24 sites

  • 1002 Eisai Trial Site

    Beijing, Beijing Municipality

  • 1006 Eisai Trial Site

    Beijing, Beijing Municipality

  • 1020 Eisai Trial Site

    Beijing, Beijing Municipality

  • 1026 Eisai Trial Site

    Beijing, Beijing Municipality

  • 1022 Eisai Trial Site

    Changchun, Jilin

  • 1016 Eisai Trial Site

    Changsha, Hunan

  • 1021 Eisai Trial Site

    Changsha, Hunan

  • 1007 Eisai Trial Site

    Chengdu, Sichuan

  • 1003 Eisai Trial Site

    Guangzhou, Guangdong

  • 1027 Eisai Trial Site

    Guilin, Guangxi

  • 1005 Eisai Trial Site

    Hangzhou, Zhejiang

  • 1012 Eisai Trial Site

    Lanzhou, Gansu

  • 1008 Eisai Trial Site

    Nanjing, Jiangsu

  • 1014 Eisai Trial Site

    Nanjing, Jiangsu

  • 1004 Eisai Trial Site

    Shanghai, Shanghai Municipality

  • 1017 Eisai Trial Site

    Shanghai, Shanghai Municipality

  • 1019 Eisai Trial Site

    Shanghai, Shanghai Municipality

  • 1015 Eisai Trial Site

    Shenyang, Liaoning

  • 1011 Eisai Trial Site

    Taiyuan, Shanxi

  • 1001 Eisai Trial Site

    Tianjin, Tianjin Municipality

  • 1010 Eisai Trial Site

    Tianjin, Tianjin Municipality

  • 1023 Eisai Trial Site

    Wuhan, Hubei

  • 1025 Eisai Trial Site

    Xiamen, Fujian

  • 1018 Eisai Trial Site

    Zhengzhou, Henan

Other trials in China

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131 I-Refractory Differentiated Thyroid Cancer in China

The primary purpose of this study is to compare the progression-free survival (PFS) of participants with radioiodine (131 I)-refractory differentiated thyroid cancer (DTC) and radiographic evidence of disease progression within the prior 12 months treated with lenvatinib 24 mg by continuous once daily (QD) oral dosing versus placebo.

Read the detailed description

This study will be conducted in 3 phases: a Prerandomization Phase, a Randomization Phase, and an Extension Phase. The Extension Phase will consist of the Optional Open Label (OOL) Lenvatinib Treatment Period and the Follow-up Period.

Being tested
Lenvatinib, Placebo
Keywords
Differentiated thyroid cancer, Chinese participants, Phase 3, Lenvatinib, E7080

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Participants will received lenvatinib 24 mg (two 10-mg capsules + one 4-mg capsule) orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor.

  • PlaceboDrug

    Participants will received lenvatinib matched placebo (two 10-mg capsules + one 4-mg capsule) orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor.

Study groups in NCT02966093
Study groupRoleWhat they receive
LenvatinibExperimentalIn the randomization phase, participants will receive lenvatinib until disease progression. Participants who discontinue due to confirmed disease progression will enter Extension Phase. Participants who discontinue without confirmed disease progression will be followed for tumor assessment until confirmed disease progression or initiation of anticancer therapy, at which time the participants will enter Follow-up period of Extension Phase.
Receives: Drug: Lenvatinib
PlaceboExperimentalIn the randomization phase, participants will receive lenvatinib matched placebo until disease progression. Participants who discontinue due to confirmed disease progression will enter Extension Phase. Participants who discontinue without confirmed disease progression will be followed for tumor assessment until confirmed disease progression or initiation of anticancer therapy, at which time the participants will enter Follow-up period of Extension Phase.
Receives: Drug: Lenvatinib; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    PFS is defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurs first) as determined by blinded independent imaging review (IIR) conducted by the imaging core laboratory using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Disease progression, per RECIST v1.1, is defined as at least a 20% relative increase and 5 millimeter (mm) absolute increase in the sum of the diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started, or the appearance of 1 or more new lesions.

    Measured: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to approximately 12 months

Secondary outcomes (3)

  1. Overall response rate (ORR)

    ORR is the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to approximately 36 months

  2. Overall survival (OS)

    OS is measured from the date of randomization until the date of death from any cause. Participants who are lost to follow-up and participants who are alive at the date of data cut-off will be censored at the date the participants were last known to be alive.

    Measured: From date of first dose of study drug until date of death from any cause or up to approximately 36 months

  3. Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

    An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs that start/increase in severity on/after the first dose of study drug up to 30 days after the final dose of study drug. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: results in death; is life threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life function; results in a congenital anomaly/birth defect; or can be defined as any other important medical event.

    Measured: For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to study completion or up to approximately 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2016 (estimated)
  2. Study start11 Jan 2017
  3. Primary completion31 Jul 2019
  4. Study completion29 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02966093
Sponsor's protocol ID
E7080-C086-308
Status last verified
Jan 2022
First submitted
15 Nov 2016
Last updated
26 Jan 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Zhu Y, Liu K, Wang K, Peng L. Vascular Endothelial Growth Factor Receptor Inhibitors in Chinese Patients With Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Network Meta-Analysis and Cost-Effectiveness Analysis. Front Endocrinol (Lausanne). 2022 Jul 14;13:909333. doi: 10.3389/fendo.2022.909333. eCollection 2022.

    PubMed 35909569

  • Zheng X, Xu Z, Ji Q, Ge M, Shi F, Qin J, Wang F, Chen G, Zhang Y, Huang R, Tan J, Huang T, Li S, Lv Z, Lin Y, Guo Z, Kubota T, Suzuki T, Ikezawa H, Gao M. A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer. Clin Cancer Res. 2021 Oct 15;27(20):5502-5509. doi: 10.1158/1078-0432.CCR-21-0761. Epub 2021 Jul 29.

    PubMed 34326132

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lenvatinib in people with Differentiated Thyroid Cancer (DTC), run by Eisai Co., Ltd. at 24 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to approximately 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02966093, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2022.

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