Lenvatinib for Recurrent Liver Cancer Post-Transplant

Recruiting at 2 trial locations

Overseen by Olumide Gbolahan

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Emory University

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, Uncontrolled illness, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial evaluates lenvatinib for the treatment of hepatocellular carcinoma (HCC) that has come back (recurrent) after a liver transplant. HCC is a cancer of the liver and is the second leading cause of cancer-related deaths in the world. Liver transplantation is a potentially curative treatment option for HCC, however, up to 20% of patients develop recurrent disease after liver transplantation and prognosis remains poor. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Systemic treatments for HCC have not been studied in patients with recurrent HCC after liver transplantation, so there is no established therapy for these patients. This phase II trial evaluates lenvatinib for this purpose.

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.

What data supports the effectiveness of the drug Lenvatinib for recurrent liver cancer after a liver transplant?

Lenvatinib has shown effectiveness in reducing tumor size and improving quality of life in patients with recurrent liver cancer after a liver transplant, as seen in a case where it helped maintain a patient's quality of life for 26 months. Additionally, it has demonstrated antiproliferative effects on liver cancer cells in laboratory and animal studies. ^{1 2 3 4 5}

Is lenvatinib safe for humans?

Lenvatinib has been studied for various cancers, including liver and thyroid cancer, and is generally considered safe, though it can cause side effects like high blood pressure, diarrhea, and fatigue. Most side effects are mild to moderate, and patients usually tolerate them well. ^{2 6 7 8 9}

How is the drug lenvatinib unique for treating recurrent liver cancer after a transplant?

Lenvatinib is unique because it targets specific proteins (receptor tyrosine kinases) involved in cancer growth, such as VEGFR and FGFR, which helps to reduce tumor size and improve patient outcomes. It is particularly notable for its use in patients with liver cancer recurrence after a liver transplant, where treatment options are limited. ^{2 4 5 10 11}

Research Team

Olumide Gbolahan

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Lenvatinib (Tyrosine Kinase Inhibitor)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

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

Findings from Research

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 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]

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]

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 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]

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 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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure? [2022]

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

Efficacy and safety of lenvatinib in patients with recurrent hepatocellular carcinoma after liver transplantation. [2023]

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

Development of a Risk Classifier to Predict Tumor Recurrence and Lenvatinib Benefits in Hepatocellular Carcinoma After Liver Transplantation. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. [2020]

5. Japan pubmed.ncbi.nlm.nih.gov

Efficient multiple treatments including molecular targeting agents in a case of recurrent hepatocellular carcinoma, post-living donor liver transplantation. [2022]

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

Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Lenvatinib in Hepatocellular Carcinoma Patients with Liver Transplantation: A Case-Control Study. [2021]

8. Australia pubmed.ncbi.nlm.nih.gov

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting. [2022]

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

The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in a real-world setting. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of lenvatinib in nonviral unresectable hepatocellular carcinoma. [2022]

11. Greece 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. [2022]