A Phase 2 Trial of Lenvatinib for the Treatment of Anaplastic Thyroid Cancer (ATC)

NCT02657369 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: E7080-M000-2132015-001929-17
• Study Type: interventional
• Target: 34
• Locations: 5 countries
• Sites: 30

Brief Summary

The primary purpose of the study is to evaluate objective response rate (\[ORR\]: complete response \[CR\] and partial response \[PR\]) by investigator review in participants with anaplastic thyroid cancer (ATC) treated with lenvatinib.

Conditions

Thyroid Carcinoma, Anaplastic

Keywords

Lenvatinib; Thyroid Cancer, Anaplastic; Lenvima; E7080

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator review using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for target lesions. CR was defined as disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameters of target lesions, taking as reference the Baseline sum diameters. Confirmation of CR or PR was performed at least 28 days following the initial achievement of the response.

  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 Outcomes (4)

• Progression-free Survival (PFS) Rate

  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)

• Overall Survival (OS) Rate

  From the date of beginning of lenvatinib administration up to date of death from any cause (up to Month 6)

• Median PFS

  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)

• Median OS

  From the date of beginning of lenvatinib administration up to date of death from any cause (up to Month 27)

Study Arms (1)

Lenvatinib

EXPERIMENTAL

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.

Drug: Lenvatinib 24 mg

Interventions

Lenvatinib 24 mg DRUG

Also known as: Lenvima, E7080

Lenvatinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• An incidental focus of medullary thyroid cancer (MTC), DTC, and/or poorly differentiated thyroid cancer in a participant with ATC is allowed.
• Histological diagnosis of ATC made through surgical resection is also acceptable.
• Prior neoadjuvant, adjuvant, or palliative chemotherapy for ATC is allowed.
• Measurable disease based on investigator's assessments meeting the following criteria:
• 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).
• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• 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.
• Adequate renal function as evidenced by calculated creatinine clearance ≥ 30 milliliter/ minute (mL/min) according to the Cockcroft and Gault formula.

You may not qualify if:

• 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.
• Newly diagnosed participants who are considered appropriate candidates for comprehensive multimodality treatment (involving surgery and/or external beam radiotherapy or chemo radiotherapy).
• 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).
• Major surgery within 2 weeks prior to the first dose of lenvatinib.
• Any anti-cancer treatment within 14 days or any investigational agent within 30 days before the first dose of study drug.
• Radiotherapy within 3 weeks prior to the first dose of lenvatinib.
• 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.
• 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.
• 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)).
• Active infection requiring systemic therapy.
• Clinically significant hemoptysis or tumor bleeding within two weeks prior to first dose of lenvatinib.
• Radiographic evidence of major blood vessel invasion/infiltration.
• 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.
• Scheduled for major surgery during the study.
• 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.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (30)

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Scottsdale, Arizona, 85259, United States

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Duarte, California, 91010, United States

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Washington D.C., District of Columbia, 20007, United States

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Washington D.C., District of Columbia, 20010, United States

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Jacksonville, Florida, 32224, United States

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Miami, Florida, 33136, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Rochester, Minnesota, 55905, United States

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New York, New York, 10065-6007, United States

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Durham, North Carolina, 27710, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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Houston, Texas, 77030, United States

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Camperdown, New South Wales, 2050, Australia

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St Leonards, New South Wales, Australia

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Caen, Calvados, 14076, France

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Bordeaux, Gironde, 33076, France

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Angers, Maine Et Loire, 49933, France

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Lyon, Rhone, 69008, France

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Lyon, Rhone, 69373, France

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Villejuif, Val De Marne, 94805, France

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Milan, 20133, Italy

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Milan, 20162, Italy

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Pisa, 56124, Italy

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Roma, 00161, Italy

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Siena, 53100, Italy

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Cardiff, South Glamorgan, CF14 2TL, United Kingdom

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Glasgow, Strathclyde, G12 OYN, United Kingdom

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Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Wirth LJ, Brose MS, Sherman EJ, Licitra L, Schlumberger M, Sherman SI, Bible KC, Robinson B, Rodien P, Godbert Y, De La Fouchardiere C, Newbold K, Nutting C, Misir S, Xie R, Almonte A, Ye W, Cabanillas ME. Open-Label, Single-Arm, Multicenter, Phase II Trial of Lenvatinib for the Treatment of Patients With Anaplastic Thyroid Cancer. J Clin Oncol. 2021 Jul 20;39(21):2359-2366. doi: 10.1200/JCO.20.03093. Epub 2021 May 7.

  PMID: 33961488 DERIVED

• Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016 Dec 3;388(10061):2783-2795. doi: 10.1016/S0140-6736(16)30172-6. Epub 2016 May 27.

  PMID: 27240885 DERIVED

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

The study was terminated since overall response rate was 3% (only 1 out of 33 participants had confirmed PR).

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2016
• First Posted: January 15, 2016
• Study Start: July 7, 2016
• Primary Completion: September 26, 2018
• Study Completion: September 26, 2018
• Last Updated: October 15, 2019
• Results First Posted: October 15, 2019

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

IT (5); AU (2); US (14); GB (3); FR (6)