Lenvatinib for Advanced Thyroid Cancer

Not currently recruiting at 2 trial locations

Overseen By Gregory Randolph, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts Eye and Ear Infirmary

Must not be taking: Anticoagulants, Antiplatelets, VEGFR-therapy

Disqualifiers: Medullary thyroid carcinoma, CNS metastasis, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called lenvatinib to determine if it can safely and effectively improve surgery outcomes for people with certain types of advanced thyroid cancer. It targets those whose cancer has spread beyond the thyroid and is difficult to remove surgically. Participants will take lenvatinib orally for a few cycles before surgery. This trial may suit individuals with specific types of thyroid cancer that make surgery risky, such as tumors affecting nearby structures like the voice box or major blood vessels. As a Phase 2 trial, it measures how well lenvatinib works in an initial, smaller group of people.

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.

Is there any evidence suggesting that lenvatinib is likely to be safe for humans?

Research has shown that lenvatinib, a drug for advanced thyroid cancer, has mixed safety results. It can be effective but also causes side effects. In a study with patients who had advanced thyroid cancer, lenvatinib was generally considered manageable. However, all patients experienced some side effects. The most common were high blood pressure and tiredness, affecting about 78% and 56% of patients, respectively.

Lenvatinib is already approved by the FDA for certain thyroid cancers, indicating it has been checked for safety in those cases. However, since this study tests lenvatinib for a different use, safety is still being closely monitored. Participants should be aware of these possible side effects and discuss any concerns with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for advanced thyroid cancer, which often includes surgery and radioactive iodine therapy, lenvatinib offers a new approach by specifically targeting the blood vessels that supply the tumor. This oral medication is a tyrosine kinase inhibitor, which blocks the signals that promote tumor growth and spread. Researchers are excited because lenvatinib has shown potential to shrink tumors and slow disease progression more effectively than existing treatments, offering hope for improved outcomes in patients with advanced thyroid cancer.

What evidence suggests that lenvatinib might be an effective treatment for advanced thyroid cancer?

Research has shown that lenvatinib, the treatment under study in this trial, effectively treats advanced thyroid cancer. In one study, about 37% of patients experienced a partial response, with their tumors shrinking, and 48% had stable disease, with no cancer growth. Another study found lenvatinib effective for various types of advanced thyroid cancer. Real-world evidence supports its use as a strong first-choice treatment, especially for thyroid cancer unresponsive to radioiodine therapy. Overall, lenvatinib has demonstrated promising results in controlling thyroid cancer growth. ^{1 3 6 7 8}

Who Is on the Research Team?

Gregory Randolph, MD

Principal Investigator

Massachusetts Eye and Ear Infirmary (MEEI)

Are You a Good Fit for This Trial?

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

Your disease can be measured using specific guidelines.

I am using or will use effective birth control during and 30 days after the study.

Ability to swallow pills

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant lenvatinib orally daily for 2, 4, or 6 cycles, each cycle being 28 days, prior to surgery

8-24 weeks

Surgery

Surgery to remove cancerous tumors (thyroidectomy) following lenvatinib treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 18 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib

Trial Overview 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.

How Is the Trial Designed?

Group I: LENVATINIB Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary

Lead Sponsor

Trials

115

Recruited

15,000+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

Lenvatinib is an effective treatment for locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer (RR-DTC), significantly improving median progression-free survival and overall response rates compared to placebo, as demonstrated in the phase 3 SELECT study with a diverse patient population.

The safety profile of lenvatinib is manageable, with hypertension being the most common side effect, but it rarely leads to treatment discontinuation, making it a viable alternative to sorafenib for patients with RR-DTC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib: A Review in Refractory Thyroid Cancer. Frampton, JE.[2018]

In a study of 23 patients with advanced thyroid cancer treated with lenvatinib over a median of 23 months, the treatment demonstrated long-term safety and efficacy, with a median progression-free survival of 25 months and overall survival of 46 months.

Most patients (21 out of 23) received lenvatinib as their first-line therapy, and while some experienced serious adverse events leading to treatment discontinuation, no drug-related deaths occurred, indicating that lenvatinib can be safely managed even in cases of slowly progressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term management of lenvatinib-treated thyroid cancer patients: a real-life experience at a single institution. Porcelli, T., Luongo, C., Sessa, F., et al.[2021]

Lenvatinib is a multitargeted receptor kinase inhibitor that effectively blocks several kinases involved in tumor growth and angiogenesis, making it a promising treatment for various solid tumors, especially differentiated thyroid cancer.

The drug has received approval in the USA for treating locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, and is currently undergoing further development and trials in multiple countries for similar indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib: first global approval. Scott, LJ.[2018]

In a phase three study involving 392 patients with differentiated thyroid cancer, lenvatinib (24 mg/day) was associated with common adverse events such as diarrhea (67%), fatigue (67%), and proteinuria (32%), which typically occurred early and were manageable through dose modifications.

Overall survival was significantly linked to the occurrence of diarrhea, with patients experiencing diarrhea having a median overall survival that was not reached, compared to 17.1 months for those without diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes. Haddad, RI., Schlumberger, M., Wirth, LJ., et al.[2019]

Lenvatinib, a multitargeted kinase inhibitor, has shown effectiveness in stabilizing progressive metastatic thyroid cancer and may improve overall survival, based on pivotal phase III trials.

While lenvatinib is a promising treatment option, it comes with a side-effect profile similar to other kinase inhibitors, necessitating careful monitoring and management of adverse events to maintain therapy continuity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal use of lenvatinib in the treatment of advanced thyroid cancer. Takahashi, S., Kiyota, N., Tahara, M.[2023]

In a retrospective study of 5 patients with unresectable anaplastic thyroid cancer (ATC), lenvatinib showed a 60% objective response rate, indicating it may be an effective treatment option for improving prognosis in this aggressive cancer.

Hypothyroidism was a common side effect, affecting 80% of patients, along with other manageable adverse effects like hypertension and fatigue, suggesting careful monitoring is needed during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib for Anaplastic Thyroid Cancer and Lenvatinib-Induced Thyroid Dysfunction. Koyama, S., Miyake, N., Fujiwara, K., et al.[2022]

In a Phase 3 study involving 392 patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib treatment resulted in a median tumor size reduction of 42.9%, with responders experiencing an even greater reduction of 51.9%.

The initial assessment at 8 weeks showed a rapid tumor size decline of 24.7%, followed by a slower continuous shrinkage, indicating that early tumor response may be a predictor of longer progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer. Robinson, B., Schlumberger, M., Wirth, LJ., et al.[2019]

Lenvatinib is effective for treating advanced thyroid cancer but can cause significant side effects like hypertension, diarrhea, and weight loss, which require careful management and monitoring.

Guidelines recommend proactive management strategies, including regular blood pressure checks and treatment breaks for adverse events, to help patients maintain optimal dosing while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert Consensus on the Management of Adverse Events During Treatment with Lenvatinib for Thyroid Cancer. Reed, N., Glen, H., Gerrard, G., et al.[2021]

Lenvatinib significantly prolongs progression-free survival (PFS) in patients with locally recurrent or metastatic radioactive iodine-refractory differentiated thyroid cancer, with a median PFS of 18.3 months compared to 3.6 months for placebo, based on a study of 392 patients.

While lenvatinib is effective, it is associated with notable adverse reactions, including hypertension and fatigue, leading to dose reductions in 68% of patients, indicating a need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lenvatinib for Progressive, Radio-iodine-Refractory Differentiated Thyroid Cancer. Nair, A., Lemery, SJ., Yang, J., et al.[2015]

Lenvatinib significantly improves progression-free survival in patients with radioiodine-resistant differentiated thyroid cancer, with a median of 18.3 months compared to 3.6 months for placebo.

The safety profile of lenvatinib is generally acceptable, with manageable side effects such as hypertension and diarrhea; however, 35-68% of patients required dose reductions, and 15% discontinued treatment due to toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of lenvatinib for thyroid cancer. Krajewska, J., Kukulska, A., Jarzab, B.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9032633/

Lenvatinib Therapy for Advanced Thyroid Cancer Efficacy outcomes are summarized in Table 2. The BOR was PR in 10 patients (37.0%), stable disease in 13 patients (48.1%), and PD in 1 patient (3.7%). No ...

2. media-us.eisai.com media-us.eisai.com/2022-10-21-Eisai-Announces-Real-World-Evidence-on-the-Clinical-Effectiveness-of-LENVIMA-R-lenvatinib-Monotherapy-for-the-Treatment-of-Patients-with-Radioiodine-Refractory-Differentiated-Thyroid-Cancer

Eisai Announces Real-World Evidence on the Clinical ... Eisai today announced final results from a real-world data (RWD) study assessing the clinical effectiveness of LENVIMA (lenvatinib) as a first-line therapy.

3. etj.bioscientifica.com etj.bioscientifica.com/view/journals/etj/12/2/ETJ-23-0003.xml

Outcomes of lenvatinib therapy in poorly differentiated thyroid ... Survival rates range between 50–85, 34–50, and 0% at 5, 10, and 15 years after diagnosis, respectively (1, 4, 5). Higher mortality rates have been associated ...

4. nature.com nature.com/articles/s44276-025-00153-2

Real-world treatment outcomes and clinicopathologic ... Our findings reinforce the clinical efficacy of lenvatinib in advanced thyroid cancer patients with heterogenous clinicopathologic/molecular features.

5. lenvimahcp.com lenvimahcp.com/rai-refractory-differentiated-thyroid-cancer

LENVIMA: Efficacy that drives results 1 Hypertension. In DTC (differentiated thyroid cancer), hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC (renal cell carcinoma), ...

6. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2018-0557

A Phase II Study of the Safety and Efficacy of Lenvatinib in ... Lenvatinib had a manageable safety profile in patients with advanced thyroid cancer (N = 51), including radioiodine-refractory differentiated thyroid cancer (RR ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35475024/

Lenvatinib Therapy for Advanced Thyroid Cancer The median progression-free survival (PFS) was 12 months (95% CI, 7.5-16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS6105

A phase 2 study of neoadjuvant lenvatinib in locally ... This phase 2 study will examine the efficacy and safety of lenvatinib prior to thyroidectomy, with the goal of achieving more favorable surgical outcomes.