Lenvatinib for Advanced Thyroid Cancer
Palo Alto (17 mi)Overseen byGregory Randolph, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts Eye and Ear Infirmary
Stay on your current meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC).
This research study involves a study drug called lenvatinib
Is the drug Lenvatinib a promising treatment for advanced thyroid cancer?Yes, Lenvatinib is a promising drug for advanced thyroid cancer. It has been approved for use in cases where the cancer does not respond to radioactive iodine. Studies have shown that it can significantly slow down the progression of the disease and improve response rates in patients.12479
What safety data is available for Lenvatinib in treating advanced thyroid cancer?Lenvatinib, also known as Lenvima, has been studied extensively for its safety profile in treating advanced thyroid cancer. Common adverse events include hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea, and stomatitis. In the SELECT trial, most patients experienced adverse events, and dose reduction was required in 35-68% of patients, although only 15% withdrew due to toxicity. Long-term safety data from real-life experiences and expert consensus highlight the need for careful management of these adverse events to ensure continued therapy.368910
What data supports the idea that Lenvatinib for Advanced Thyroid Cancer is an effective drug?The available research shows that Lenvatinib is effective for treating advanced thyroid cancer. In a large study, patients who took Lenvatinib had a longer time before their cancer got worse compared to those who took a placebo, which is a pill with no medicine in it. This study involved 392 patients and showed that Lenvatinib significantly delayed the progression of the disease. Additionally, the drug has been approved by the FDA for this specific type of thyroid cancer, indicating its effectiveness. Overall, these findings suggest that Lenvatinib is a beneficial option for patients with advanced thyroid cancer.125910
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you've had anticoagulant or antiplatelet therapy (except aspirin 81 mg daily) within 30 days prior to the study. It's best to discuss your current medications with the study team.
Eligibility Criteria
This trial is for adults with advanced thyroid cancer who can swallow pills, have controlled blood pressure, and are not pregnant or breastfeeding. They must agree to use effective contraception and cannot have had certain treatments or conditions that would interfere with the study.Inclusion Criteria
I am 18 or older and can sign the consent form.
I am very active and have no medical reasons preventing surgery.
Exclusion Criteria
I have a condition that affects how my body absorbs medication.
I have been diagnosed with a specific type of thyroid cancer.
I have previously been treated with lenvatinib or a similar drug.
I am not pregnant or breastfeeding.
I am currently being treated for an infection.
I have not had a blood clot in the past year.
My heart's electrical activity is normal, with no significant ECG abnormalities.
My scans show a tumor inside my airway or surrounding my carotid artery.
My cancer has spread to my brain or spinal cord.
I have had radiation therapy to my neck before.
I do not have serious heart problems like recent heart failure, heart attack, or stroke.
Treatment Details
The trial is testing lenvatinib's safety and effectiveness before surgery in patients with invasive extrathyroidal differentiated thyroid cancer. It aims to see if this drug improves surgical outcomes.
1Treatment groups
Experimental Treatment
Group I: LENVATINIBExperimental Treatment1 Intervention
Study procedures include screening for eligibility and study treatment, evaluations, and follow up visits
* Lenvatinib will be administered orally daily at a predetermined dose for 2, 4, or 6 cycles, dependent on response. 1 cycle is 28 days.
* Surgery per standard of care will follow lenvatinib treatment.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
MD Anderson Cancer CenterHouston, TX
Massachusetts General Hospital Cancer CenterBoston, MA
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Who is running the clinical trial?
Massachusetts Eye and Ear InfirmaryLead Sponsor
Eisai Inc.Industry Sponsor
References
Lenvatinib: first global approval. [2018]Lenvatinib (Lenvima™) is a multitargeted receptor kinase inhibitor that inhibits the kinase activities of vascular endothelial-derived growth factor receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor α, RET and KIT. In addition to their role in normal cellular function, these kinases have been implicated in pathogenic angiogenesis, tumour growth and cancer progression. Lenvatinib is being developed by Eisai Co. Ltd for the treatment of solid tumours, primarily for differentiated thyroid cancer, and other malignancies. A capsule formulation of the drug has received approval in the USA for use in locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. Lenvatinib is in pre-registration for this indication in the EU, Australia, Brazil, Canada, Japan, South Korea, Russia, Singapore and Switzerland, and is in phase 3 development in Argentina, Chile and Thailand. Lenvatinib has orphan designation in the EU and Japan for use in differentiated thyroid cancer. In addition, an ongoing global, phase 3 trial is evaluating the use of lenvatinib as first-line treatment in unresectable hepatocellular carcinoma. This article summarizes the milestones in the development of lenvatinib leading to this first approval in locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.
FDA Approval Summary: Lenvatinib for Progressive, Radio-iodine-Refractory Differentiated Thyroid Cancer. [2015]The FDA approved lenvatinib (Lenvima, Eisai Inc.) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory (RAI-refractory) differentiated thyroid cancer (DTC). In an international, multicenter, double-blinded, placebo-controlled trial (E7080-G000-303), 392 patients with locally recurrent or metastatic RAI-refractory DTC and radiographic evidence of disease progression within 12 months prior to randomization were randomly allocated (2:1) to receive either lenvatinib 24 mg orally per day (n = 261) or matching placebo (n = 131) with the option for patients on the placebo arm to receive lenvatinib following independent radiologic confirmation of disease progression. A statistically significant prolongation of progression-free survival (PFS) as determined by independent radiology review was demonstrated [HR, 0.21; 95% confidence interval (CI), 0.16-0.28; P
Drug safety evaluation of lenvatinib for thyroid cancer. [2015]Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR1,2,3,4, FGFR1,2,3,4, PDGFR-α as well as RET and KIT signaling network. Its activity against radioiodine-resistant differentiated thyroid cancer (DTC) has been recently demonstrated. Patients, who were given lenvatinib, showed significantly longer median progression free survival than placebo group, 18.3 vs 3.6 months, respectively. This review is focused on lenvatinib safety profile in patients treated due to DTC and medullary thyroid carcinoma. Among the most frequent lenvatinib-related adverse events (AEs) were hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea and stomatitis. Although a lot of them were manageable, in 35-68% of patients dose reduction was required. Nevertheless, only 15% of subjects withdrew the drug due to its toxicity.
Lenvatinib: A Review in Refractory Thyroid Cancer. [2018]Lenvatinib (Lenvima®) is an oral, multi-targeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor alpha, and RET and KIT signalling networks, which are implicated in tumour growth and maintenance. In the EU and USA, lenvatinib is indicated for the treatment of locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer (RR-DTC). This approval was based on the results of the randomized, double-blind, multinational, phase 3 SELECT study, in which lenvatinib significantly improved median progression-free survival (PFS) and overall response rate compared with placebo in patients with RR-DTC. The PFS benefit with lenvatinib was seen in all pre-specified subgroups, including patients who had received either one or no prior VEGF-targeted therapy. Moreover, the PFS benefit with lenvatinib was maintained regardless of BRAF or RAS mutation status. The safety and tolerability profile of lenvatinib in SELECT was consistent with that of other VEGF/VEGF receptor-targeted therapies and was mostly manageable. Hypertension was the most common treatment-related adverse event in lenvatinib-treated patients, but only infrequently led to discontinuation of the drug. Although not collected in SELECT, information on quality of life would be useful in assessing the overall impact of therapy on the patient. This notwithstanding, the data which are available indicate that lenvatinib is an effective and generally well-tolerated treatment option for patients with RR-DTC. Lenvatinib, therefore, offers an acceptable alternative to sorafenib--currently, the only other TKI approved for this indication.
Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer. [2019]Lenvatinib improved the progression-free survival (PFS) and overall response rate of patients with radioiodine-refractory differentiated thyroid cancer vs placebo in the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT).
Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes. [2019]In the study of (E7080) lenvatinib in differentiated cancer of the thyroid, most patients experienced an adverse event. In this report, we examine common lenvatinib-emergent adverse events in this phase three, randomized, double-blind study.
Lenvatinib for Anaplastic Thyroid Cancer and Lenvatinib-Induced Thyroid Dysfunction. [2022]Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has an anticancer action in patients with differentiated thyroid cancer that is refractory to radioiodine. Knowledge of the efficacy and safety of lenvatinib in patients with anaplastic thyroid cancer (ATC) is limited. Tyrosine kinase inhibitors frequently cause hypothyroidism, but the incidence of hypothyroidism with lenvatinib is unclear.
Optimal use of lenvatinib in the treatment of advanced thyroid cancer. [2023]The development of orally active, multitargeted kinase inhibitors (MKIs) represents a significant advance in the treatment of progressive, metastatic thyroid cancer. Lenvatinib, an MKI targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and RET, has shown efficacy in stabilizing previously progressive disease, with emerging evidence of a possible benefit in terms of overall survival. However, lenvatinib is associated with a side-effect profile similar to those of other MKIs that might affect the outcome of therapy. The aim of this review is to summarize the clinical efficacy and safety of MKIs in the treatment of advanced thyroid cancer in pivotal phase III trials. Common adverse events that may occur during lenvatinib therapy and their management are discussed, including conditions in which its administration should be temporarily withdrawn and resumed pending resolution of adverse events. We focus on data from a subanalysis of Japanese patients in the SELECT trial and in a post-marketing study in Japan. We suggest that lenvatinib is a valuable treatment option for advanced differentiated thyroid cancer. Monitoring and careful management of adverse events including supportive care are required to ensure continuation of therapy.
Expert Consensus on the Management of Adverse Events During Treatment with Lenvatinib for Thyroid Cancer. [2021]Lenvatinib is an oral multi-kinase inhibitor approved for the treatment of adults with progressive, locally advanced or metastatic, differentiated thyroid carcinoma refractory to radioactive iodine.
Long-term management of lenvatinib-treated thyroid cancer patients: a real-life experience at a single institution. [2021]The efficacy of lenvatinib for advanced and progressive radioactive iodine refractory differentiated thyroid cancer is well established. Herein, we retrospectively evaluated the long-term safety and efficacy of lenvatinib in 23 patients treated at a single Institution.