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

NCT02966093 | Completed Phase 3 DMC

• 1 other identifier: E7080-C086-308
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 24

Brief 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 versus placebo.

Conditions

Differentiated Thyroid Cancer (DTC)

Keywords

Differentiated thyroid cancer; Chinese participants; Phase 3; Lenvatinib; E7080

Outcome Measures

Primary Outcomes (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.

  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)

• Overall response rate (ORR)

  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

• Overall survival (OS)

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

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

  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

Study Arms (2)

Lenvatinib

EXPERIMENTAL

In 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.

Drug: Lenvatinib

Placebo

EXPERIMENTAL

In 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.

Drug: Lenvatinib; Drug: Placebo

Interventions

Lenvatinib DRUG

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.

Lenvatinib; Placebo

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed diagnosis of one of the following Differentiated Thyroid Cancer (DTC) subtypes:
• a. 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.
• 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.

You may not qualify if:

• 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).
• 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)

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (24)

1002 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

1006 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

1020 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

1026 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

1025 Eisai Trial Site

Xiamen, Fujian, China

Location

1012 Eisai Trial Site

Lanzhou, Gansu, China

Location

1003 Eisai Trial Site

Guangzhou, Guangdong, China

Location

1027 Eisai Trial Site

Guilin, Guangxi, China

Location

1018 Eisai Trial Site

Zhengzhou, Henan, China

Location

1023 Eisai Trial Site

Wuhan, Hubei, China

Location

1016 Eisai Trial Site

Changsha, Hunan, China

Location

1021 Eisai Trial Site

Changsha, Hunan, China

Location

1008 Eisai Trial Site

Nanjing, Jiangsu, China

Location

1014 Eisai Trial Site

Nanjing, Jiangsu, China

Location

1022 Eisai Trial Site

Changchun, Jilin, China

Location

1015 Eisai Trial Site

Shenyang, Liaoning, China

Location

1004 Eisai Trial Site

Shanghai, Shanghai Municipality, China

Location

1017 Eisai Trial Site

Shanghai, Shanghai Municipality, China

Location

1019 Eisai Trial Site

Shanghai, Shanghai Municipality, China

Location

1011 Eisai Trial Site

Taiyuan, Shanxi, China

Location

1007 Eisai Trial Site

Chengdu, Sichuan, China

Location

1001 Eisai Trial Site

Tianjin, Tianjin Municipality, China

Location

1010 Eisai Trial Site

Tianjin, Tianjin Municipality, China

Location

1005 Eisai Trial Site

Hangzhou, Zhejiang, China

Location

Related Publications (2)

• 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.

  PMID: 35909569 DERIVED

• 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.

  PMID: 34326132 DERIVED

MeSH Terms

Interventions

lenvatinib

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 17, 2016
• Study Start: January 11, 2017
• Primary Completion: July 31, 2019
• Study Completion: December 29, 2021
• Last Updated: January 26, 2022

Record last verified: 2022-01

Locations

CN (24)