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NCT02657369

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

Terminated Phase 2 Results posted Last updated 15 October 2019
What this trial tests

Phase 2 trial testing Lenvatinib 24 mg in Thyroid Carcinoma, Anaplastic in 34 participants. Terminated before completion.

Timeline
7 July 2016
Primary endpoint
26 September 2018
26 September 2018

Quick facts

Lead sponsorEisai Inc.
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment34
Start date7 July 2016
Primary completion26 September 2018
Estimated completion26 September 2018
Sites30 locations across France, Italy, United Kingdom, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Eisai Inc. — full company profile →

Who can join

Adults 18 to 99, any sex, with Thyroid Carcinoma, Anaplastic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Primary · 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)

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.

GroupValue95% CI
Lenvatinib 24 mg3.00.1 – 15.8
Progression-free Survival (PFS) Rate Secondary · 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)

Twelve-week PFS rate was the percentage of participants in the analysis population who remain alive and progression-free at 12 weeks. PFS was defined as the time from the date of beginning of lenvatinib administration to the date of first documentation of confirmed disease progression or death, whichever occurred first. The Kaplan-Meier estimated rate method was used to estimate 12-week PFS, along with the corresponding 95% confidence interval (CI). Participants who were off study due to lost to follow up, withdrew consent, or study terminated by sponsor, had new anti-cancer treatment, had no

GroupValue95% CI
Lenvatinib 24 mg36.420.6 – 52.3
Overall Survival (OS) Rate Secondary · From the date of beginning of lenvatinib administration up to date of death from any cause (up to Month 6)

Six-month OS rate was defined as the percentage of participants in the analysis population who are alive at 6 months. OS was defined as the time from the date of beginning of lenvatinib administration until date of death from any cause. The Kaplan-Meier estimated rate method was used to estimate six-month OS, along with the corresponding 95% CI. Participants with last known alive date as study terminated by sponsor were censored.

GroupValue95% CI
Lenvatinib 24 mg41.224.8 – 56.9
Median PFS Secondary · 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)

PFS was defined as the time from the date of beginning of lenvatinib administration to the date of first documentation of confirmed disease progression or death, whichever occurs first. Median PFS was estimated using the Kaplan-Meier method. Participants who were off study due to lost to follow up, withdrew consent, or study terminated by sponsor, had new anti-cancer treatment, had no baseline/post-baseline tumor assessments, or missed 2 or more visits prior to event were censored.

GroupValue95% CI
Lenvatinib 24 mg2.61.4 – 2.8
Median OS Secondary · From the date of beginning of lenvatinib administration up to date of death from any cause (up to Month 27)

OS was defined as the time from the date of beginning of lenvatinib administration until date of death from any cause. Median OS was estimated using the Kaplan-Meier method. Participants with last known alive date as study terminated by sponsor were censored.

GroupValue95% CI
Lenvatinib 24 mg3.22.8 – 8.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From signature of informed consent form up to 28 days after last dose of study drug (up to Month 27). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lenvatinib
Serious: 25/34 (74%)
Deaths: 27/34

Serious adverse events (44 terms)

ReactionSystemLenvatinib
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
PresyncopeNervous system disorders
DysphagiaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Deep vein thrombosisVascular disorders
Malignant pleural effusionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to peritoneumNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Chest painGeneral disorders
Non-cardiac chest painGeneral disorders
Confusional statePsychiatric disorders
Accidental overdoseInjury, poisoning and procedural complications
Cardiopulmonary failureCardiac disorders
Abdominal lymphadenopathyBlood and lymphatic system disorders
AgranulocytosisBlood and lymphatic system disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Laryngeal oedemaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Other adverse events (189 terms — click to expand)

ReactionSystemLenvatinib
HypertensionVascular disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
StomatitisGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Weight decreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
ProteinuriaRenal and urinary disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
DysphagiaGastrointestinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypothyroidismEndocrine disorders
AstheniaGeneral disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
HyperglycaemiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Back painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
InsomniaPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood thyroid stimulating hormone increasedInvestigations
International normalised ratio increasedInvestigations
DysgeusiaNervous system disorders
Ear painEar and labyrinth disorders
Abdominal painGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders

Most-reported serious reactions: Malignant neoplasm progression, Dyspnoea, Pulmonary embolism, Hypertension, Asthenia, Pyrexia, Presyncope, Dysphagia.

Data from ClinicalTrials.gov NCT02657369 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Therapeutic advances in anaplastic thyroid cancer: a current perspective.
    Saini S, Tulla K, Maker AV, Burman KD, et al · · 2018 · cited 168× · PMID 30352606 · DOI 10.1186/s12943-018-0903-0
  2. Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma.
    Iyer PC, Dadu R, Gule-Monroe M, Busaidy NL, et al · · 2018 · cited 162× · PMID 29996921 · DOI 10.1186/s40425-018-0378-y
  3. Lenvatinib for Anaplastic Thyroid Cancer.
    Tahara M, Kiyota N, Yamazaki T, Chayahara N, et al · · 2017 · cited 135× · PMID 28299283 · DOI 10.3389/fonc.2017.00025
  4. Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment.
    Capozzi M, De Divitiis C, Ottaiano A, von Arx C, et al · · 2019 · cited 100× · PMID 31118801 · DOI 10.2147/cmar.s188316
  5. Open-Label, Single-Arm, Multicenter, Phase II Trial of Lenvatinib for the Treatment of Patients With Anaplastic Thyroid Cancer.
    Wirth LJ, Brose MS, Sherman EJ, Licitra L, et al · · 2021 · cited 97× · PMID 33961488 · DOI 10.1200/jco.20.03093
  6. Real-World Experience with Targeted Therapy for the Treatment of Anaplastic Thyroid Carcinoma.
    Iyer PC, Dadu R, Ferrarotto R, Busaidy NL, et al · · 2018 · cited 96× · PMID 29161986 · DOI 10.1089/thy.2017.0285
  7. American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group consensus statement on mutational testing in thyroid cancer: Defining advanced thyroid cancer and its targeted treatment.
    Shonka DC, Ho A, Chintakuntlawar AV, Geiger JL, et al · · 2022 · cited 80× · PMID 35274388 · DOI 10.1002/hed.27025
  8. Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice.
    Tirrò E, Martorana F, Romano C, Vitale SR, et al · · 2019 · cited 63× · PMID 31540307 · DOI 10.3390/genes10090709

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