Lenvatinib + TACE for Liver Cancer

Overseen By Shondra Word

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Antivirals

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Hypertension, Cardiovascular impairment, 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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of lenvatinib, a cancer drug, and a procedure called transcatheter arterial chemoembolization (TACE) to determine if they can better prepare patients with liver cancer for a transplant. The focus is on patients with hepatocellular carcinoma (HCC) that doesn't meet the typical transplant criteria. The trial will compare results with patients who have already undergone a transplant under similar conditions. Suitable candidates have liver cancer beyond the usual transplant criteria, have not received prior treatment, and are on the liver transplant waiting list. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have hepatitis B or C, you must continue antiviral therapy while on the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using lenvatinib with TACE, a liver cancer treatment, is generally safe. In studies with liver cancer patients, this combination proved more effective than TACE alone. Patients tolerated it well, and side effects were typical for cancer treatments. Some changes in liver function occurred, but they were not serious. These results suggest a positive safety outlook for using lenvatinib with TACE. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver cancer?

Researchers are excited about combining lenvatinib with Transcatheter Arterial Chemoembolization (TACE) for liver cancer because this approach offers a novel way to tackle tumors. While standard treatments like surgery or systemic therapies focus on removing or shrinking tumors, lenvatinib is an oral medication that targets specific growth factors involved in tumor development, potentially slowing cancer progression more effectively. When paired with TACE, which directly delivers chemotherapy to the liver, this combination could enhance the treatment's ability to control liver tumors, offering new hope for patients with hepatocellular carcinoma beyond traditional criteria for transplant eligibility.

What evidence suggests that lenvatinib in combination with TACE might be an effective treatment for liver cancer?

Research has shown that using lenvatinib with transcatheter arterial chemoembolization (TACE) may be promising for treating liver cancer. In this trial, participants will receive a six-month regimen of neoadjuvant lenvatinib combined with TACE before liver transplantation. One study found that this combination effectively managed liver cancer in patients unsuitable for a transplant. Patients who received both treatments experienced noticeable tumor shrinkage. Another study observed that starting TACE early, along with lenvatinib, led to better results than using lenvatinib alone. Overall, these findings suggest that this combined treatment could be an effective option for liver cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Maen Abdelrahim, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer (HCC) who haven't had previous cancer treatments, are on the liver transplant list, and can perform daily activities with little to no assistance. They must have well-managed hepatitis if present, good organ function, not be pregnant or breastfeeding, and agree to use effective contraception.

Inclusion Criteria

My organs and bone marrow are functioning well.

I am a man who can father children and will use condoms or other effective birth control.

I am an adult with liver cancer that has progressed beyond early stages.

Exclusion Criteria

I am not pregnant, breastfeeding, allergic to lenvatinib, and I agree to use contraception.

My high blood pressure is not controlled despite taking medication.

I have a bleeding or clotting disorder, or I'm at high risk for severe bleeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive a six-month regimen of lenvatinib in combination with TACE prior to liver transplantation

6 months

Monthly visits for TACE and lenvatinib administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Monthly visits for monitoring

Transplantation and Post-Transplant Follow-up

Participants undergo liver transplantation and are monitored for outcomes such as tumor necrosis and survival

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Transcatheter Arterial Chemoembolization

Trial Overview

The study tests a combination of Lenvatinib medication and TACE procedure over six months before a liver transplant in patients with large HCC tumors. It aims to compare these patients' outcomes against those from past records who didn't receive this treatment.

How Is the Trial Designed?

Group I: Matched Historical Control Patients Experimental Treatment 1 Intervention

Historical controls will be liver transplant recipients matched on age, etiology of liver disease (viral vs. non-viral), listing tumor size, and number of TACE procedures to cases in the intervention group who receive a transplant.

Group II: Lenvatinib in Combination with TACE Prior to Liver Transplantation Experimental Treatment 2 Interventions

Regimen of six months neoadjuvant lenvatinib in combination with TACE prior to liver transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan Criteria.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

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

In a study of 247 patients with unresectable hepatocellular carcinoma, LEN-TACE sequential therapy showed significantly better overall survival and progression-free survival compared to LEN monotherapy, indicating its enhanced efficacy.

The objective response rate for LEN-TACE was 61.9%, and the study found that a positive initial response to LEN treatment was a key factor in achieving a deep response during sequential therapy, suggesting that prior treatment response can guide future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective Response by mRECIST to Initial Lenvatinib Therapy Is an Independent Factor Contributing to Deep Response in Hepatocellular Carcinoma Treated with Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy. Kuroda, H., Oikawa, T., Ninomiya, M., et al.[2022]

Lenvatinib is an effective multikinase inhibitor approved for treating radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma, showing favorable efficacy in various malignancies.

While lenvatinib has beneficial effects, it is associated with common adverse events like hypertension and fatigue, necessitating careful monitoring and management to enhance patient quality of life and treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Cabanillas, ME., Takahashi, S.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9274079/

Efficacy and safety of transcatheter arterial ...

This study provided important clinical results. We retrospectively analyzed 30 HCC patients to evaluate the efficacy and safety of TACE-lenvatinib sequential ...

2.

spandidos-publications.com

spandidos-publications.com/10.3892/mco.2024.2761

Efficacy of lenvatinib and transarterial chemoembolization ...

Therefore, the results of the present study revealed that early TACE should be considered instead of continuing lenvatinib only treatment in ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04997850

Study Details | NCT04997850 | The Safety and Efficacy of ...

We adopted the prospective cohort study to compare the safety and efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Programmed Cell Death ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.417

Transcatheter arterial chemoembolization therapy in ...

In this final analysis, the combination of TACE and lenvatinib showed promising therapeutic efficacy in patients with uHCC. No new safety signal was observed.

5.

nature.com

nature.com/articles/s41392-024-01991-1

Envafolimab plus lenvatinib and transcatheter arterial ...

This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9068979/

Efficacy and Safety of TACE Combined With Lenvatinib ...

Compared with TACE, the combination treatment demonstrated an improved clinical efficacy and manageable safety profile in patients with uHCC.

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.478

The efficacy and safety of transarterial chemoembolization ...

The average number of TACE procedures per patient was 1.70. The median PFS and OS were not reached, while the 6-month PFS rate was 77.1% (95% CI ...