Lenvatinib for Advanced Thyroid Cancer

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

30 Participants Needed

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

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.

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. ^{1 2 3 4 5}

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. ^{5 6 7 8 9}

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. ^{2 5 6 9 10}

Research Team

Gregory Randolph, MD

Principal Investigator

Massachusetts Eye and Ear Infirmary (MEEI)

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Lenvatinib: first global approval. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Expert Consensus on the Management of Adverse Events During Treatment with Lenvatinib for Thyroid Cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lenvatinib for Progressive, Radio-iodine-Refractory Differentiated Thyroid Cancer. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term management of lenvatinib-treated thyroid cancer patients: a real-life experience at a single institution. [2021]

6. United States 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. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Optimal use of lenvatinib in the treatment of advanced thyroid cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of lenvatinib for thyroid cancer. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Lenvatinib for Anaplastic Thyroid Cancer and Lenvatinib-Induced Thyroid Dysfunction. [2022]

10. France pubmed.ncbi.nlm.nih.gov

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