Lenvatinib for Recurrent Liver Cancer Post-Transplant

Recruiting at 2 trial locations

Overseen By Olumide B. Gbolahan, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, Uncontrolled illness, others

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: 90

Duration: Indefinite, until disease progression or unacceptable toxicity

19 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates lenvatinib for treating hepatocellular carcinoma (HCC) that has returned after a liver transplant. Lenvatinib blocks certain enzymes that promote cancer cell growth. Currently, no standard treatment exists for this condition, so the trial aims to determine lenvatinib's effectiveness. Individuals who have had a liver transplant and face a recurrence of liver cancer that cannot be surgically removed might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that you should not be on any other investigational agents or have had certain treatments recently. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research shows that lenvatinib is generally well-tolerated by patients with liver cancer. In studies involving individuals whose liver cancer returned after a liver transplant, lenvatinib proved to be safe. Although some side effects occurred, they were mostly manageable. This drug already has approval for other types of liver cancer, indicating a history of safety. However, as this is a phase II study, more information is needed to fully understand its safety for this specific use. It's important to remember that reactions vary, so some people might experience more side effects than others. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about lenvatinib for recurrent liver cancer post-transplant because it offers a novel angle of attack against the disease. Unlike standard treatments like immunosuppressive therapy, lenvatinib is a targeted therapy that inhibits specific proteins called tyrosine kinases, which are involved in tumor growth and blood supply. This mechanism can potentially slow cancer progression more effectively. Additionally, lenvatinib is taken orally, making it a convenient option compared to some existing treatments that require intravenous administration. These unique features position lenvatinib as a promising candidate in the ongoing search for better liver cancer treatments post-transplant.

What evidence suggests that lenvatinib might be an effective treatment for recurrent liver cancer?

Research has shown that lenvatinib, the treatment under study in this trial, can effectively treat liver cancer that returns after a transplant. In one study, about 20% of patients experienced tumor shrinkage with lenvatinib, meaning one in five patients saw improvement. Another study suggested that lenvatinib might be safer and just as effective as sorafenib, another drug for this cancer type, potentially leading to better survival rates. Additionally, lenvatinib might lower the risk of cancer returning in people with certain risk factors, such as having multiple tumors or tumors that differ significantly from normal cells. While more research is needed, these findings suggest lenvatinib could be a promising option for liver cancer that recurs after a transplant. ^{2 3 5 6 7}

Who Is on the Research Team?

Olumide Gbolahan

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

Adults with recurrent hepatocellular carcinoma after liver transplant, who are in good physical condition (ECOG <=1), have measurable disease, and a life expectancy over 12 weeks. They must not be planning surgery, have brain metastases or uncontrolled illnesses like heart failure. Participants need normal organ function tests and agree to use contraception.

Inclusion Criteria

My white blood cell count is healthy without recent medical help.

I have a heart condition or have been treated with heart-toxic drugs and have been assessed for heart function.

Total bilirubin =< 3 times the institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)

Exclusion Criteria

I do not have serious heart problems like recent heart attacks or severe heart failure.

I have recovered from side effects of previous cancer treatments and surgeries.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib orally once daily. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the protocol therapy.

Indefinite, until disease progression or unacceptable toxicity

Monthly visits for treatment assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 90 days until death or 2 years from registration.

Up to 2 years

Every 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib

Trial Overview

The trial is testing Lenvatinib's effectiveness for patients whose liver cancer has returned post-transplant. It aims to block enzymes that tumor cells need to grow since there's no established treatment for this recurrence.

How Is the Trial Designed?

Group I: Treatment (Lenvatinib) Experimental Treatment 2 Interventions

Patients receive lenvatinib PO QD. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the protocol therapy

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Eisai Co., Ltd.

Industry Sponsor

Trials

182

Recruited

660,000+

Lynn Kramer

Eisai Co., Ltd.

Chief Medical Officer since 2019

MD from the University of Tokyo

Haruo Naito

Eisai Co., Ltd.

Chief Executive Officer since 1988

Bachelor's degree in Economics from Keio University

Published Research Related to This Trial

In a study of 67 patients with unresectable advanced hepatocellular carcinoma (HCC), lenvatinib (LEN) showed a higher objective response rate and significantly longer progression-free survival in patients with nonviral causes (alcohol and NASH) compared to those with viral causes (HCV and HBV).

The median overall survival was also significantly better in the nonviral group, indicating that LEN may be a more effective treatment option for nonviral HCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of lenvatinib in nonviral unresectable hepatocellular carcinoma. Tomonari, T., Sato, Y., Tanaka, H., et al.[2022]

A 62-year-old man with recurrent hepatocellular carcinoma after liver transplantation experienced long-term survival (26 months) while treated with the molecular targeting therapy lenvatinib, which effectively reduced tumor volumes and alpha-fetoprotein levels.

This case suggests that multidisciplinary treatment, including lenvatinib, may be a viable option for managing recurrent hepatocellular carcinoma post-transplantation, although complications like sepsis ultimately led to the patient's death 73 months after recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient multiple treatments including molecular targeting agents in a case of recurrent hepatocellular carcinoma, post-living donor liver transplantation. Suzuki, R., Goto, R., Kawamura, N., et al.[2022]

Lenvatinib effectively inhibits the growth of liver cancer cells in vitro and in vivo, with its efficacy varying based on the expression levels of specific receptors (FGFR1-4, RET) in the cancer cells.

In animal models, lenvatinib reduced tumor growth by significantly decreasing blood vessel formation (angiogenesis) and increasing tumor necrosis, although it did not induce apoptosis in the cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Ogasawara, S., Mihara, Y., Kondo, R., et al.[2020]

In a study of 10 patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation, lenvatinib demonstrated a disease control rate of 70%, with a median overall survival of 16.4 months, indicating its potential effectiveness in this patient population.

Lenvatinib was found to have a similar safety profile and efficacy in both liver transplant (LT) and non-liver transplant (non-LT) patients, with most adverse events being mild (grade 1-2), suggesting it can be safely used in post-transplant HCC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Lenvatinib in Hepatocellular Carcinoma Patients with Liver Transplantation: A Case-Control Study. Chen, YY., Chen, CL., Lin, CC., et al.[2021]

In a study of 45 patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation, lenvatinib demonstrated an objective response rate of 20% and a median overall survival of 14.5 months, indicating its potential efficacy in this patient population.

Patients with better liver function (ALBI grade 1) had significantly improved overall survival (52.3 months) compared to those with poorer liver function (ALBI grade 2), highlighting the importance of liver health in treatment outcomes with lenvatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenvatinib in patients with recurrent hepatocellular carcinoma after liver transplantation. Bang, K., Casadei-Gardini, A., Yoo, C., et al.[2023]

A new risk classifier, the Risk Classifier of South China Cohort (RCOSC), was developed using data from 287 liver transplant patients with hepatocellular carcinoma (HCC) and showed strong predictive performance for HCC recurrence (C-statistic of 0.866).

The RCOSC outperformed existing selection criteria (Milan, Up-to-7, and UCSF) in identifying high-risk patients who may benefit from adjuvant therapy with lenvatinib, suggesting it can enhance clinical decision-making for post-transplant HCC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a Risk Classifier to Predict Tumor Recurrence and Lenvatinib Benefits in Hepatocellular Carcinoma After Liver Transplantation. Deng, Y., Yang, J., Chen, Y., et al.[2023]

In a study of 99 patients with unresectable hepatocellular carcinoma (u-HCC), continuing lenvatinib (LEN) treatment beyond disease progression significantly improved overall survival compared to stopping treatment, with median survival times of 10.8 months versus 5.8 months, respectively.

Factors such as maintaining good performance status and experiencing hand-foot skin reactions during LEN treatment were associated with better outcomes, suggesting that continuing LEN may be a viable option for patients who tolerate it well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure? Hiraoka, A., Kumada, T., Tada, T., et al.[2022]

In a real-world study of 16 patients with advanced hepatocellular carcinoma, lenvatinib demonstrated a 40% objective response rate, indicating its efficacy in treating this condition after prior treatments.

The treatment was generally safe, with manageable adverse events such as fatigue, hypertension, and proteinuria, which could be controlled through dose adjustments and supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in a real-world setting. Obi, S., Sato, T., Sato, S., et al.[2020]

Lenvatinib was effectively used to treat unresectable recurrences of hepatocellular carcinoma (HCC) in two patients who had previously undergone liver transplantation, showing a complete response for 12 months in one case and a partial response for 5 months in the other.

No severe adverse events were reported during the treatment, indicating that lenvatinib may be a safe option for managing HCC recurrences after liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Lenvatinib for the Treatment of Recurrent Hepatocellular Carcinoma After Living Donor Liver Transplantation: A Report of Two Cases. Ichida, A., Akamatsu, N., Nagata, R., et al.[2022]

In a real-world study of 41 patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib, the objective response rate was 61.2%, indicating a high early response rate and effectiveness of the treatment.

The safety profile of lenvatinib was consistent across patients who met and did not meet the REFLECT trial inclusion criteria, suggesting that lenvatinib is tolerable even in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting. Sho, T., Suda, G., Ogawa, K., 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

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This phase II study aims evaluate the safety and efficacy of lenvatinib in patients with recurrent HCC after liver transplantation.

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A Comparative Outcome and Safety Analysis of Lenvatinib ...

Our findings suggest that lenvatinib is a safer option as compared to sorafenib for patients with HCC recurrence after LT, granting a comparable survival with a ...

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cda-amc.ca

cda-amc.ca/sites/default/files/pdf/htis/2024/RC1553-Lenvatinibin-HCC-Post-Transplant.pdf

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The single-arm chart review study showed lenvatinib treatment had an overall response rate (ORR) of 20.0%, a median overall survival (OS).

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Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib ...

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ar.iiarjournals.org

ar.iiarjournals.org/content/42/2/1161

Efficacy and Safety of Lenvatinib for the Treatment ...

We report two cases of unresectable HCC recurrences after living donor LT that were treated effectively and safely with lenvatinib.