Liver Link Intervention for Liver Cancer

Overseen By Regina Weber

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Disqualifiers: Age over 75, BMI over 50, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial investigators for guidance.

Is the Liver Link treatment generally safe for humans?

The safety of treatments like Liver Link, which may involve antibody-drug conjugates or immune checkpoint inhibitors, can be a concern due to potential liver-related side effects. These treatments have been associated with drug-induced liver injury (DILI) and immune-related adverse events (irAEs), which can be serious and sometimes require stopping the treatment. ^{1 2 3 4 5}

How is the Liver Link treatment different from other liver cancer treatments?

Liver Link is unique because it may involve a novel approach or combination of methods not typically used in standard treatments for liver cancer, such as traditional Chinese medicine injections or interventional therapies, which are emerging as new treatment options. ^{6 7 8 9 10}

What is the purpose of this trial?

Mortality rates for hepatocellular carcinoma (HCC) have risen in the US over the past two decades, disproportionately impacting Black patients with chronic liver disease5,6. Black patients are 50% less likely than White patients to receive curative therapies for HCC even when presenting with early stage disease7,8. Reasons for disparities in mortality are in part related to failure to progress through the complex HCC care continuum to access curative therapies as a result of the unequal distribution of social and structural determinants of health (SSDOH)9,10. SSDOH are the social conditions that influence individual and group differences in health11. For example, investigators found that Black patients with early stage HCC were more likely than White patients to have ongoing alcohol and substance and as a result were not candidates for liver transplantation (LT)7. In addition, data from our prospective cohort study demonstrated that Black patients with HCC have a higher burden of poor SSDOH that than their White counterparts, including higher rates of poverty, educational achievement less than high school and lapses in subspecialty care. The downstream consequences of these inequities including poor health-related knowledge and social needs are being increasingly targeted for improvement by hospital systems and providers in cancer care. However, there are currently no interventions designed to target social determinants or downstream social needs and eliminate racial disparities in HCC care. Successful health disparities interventions have been culturally tailored and multi-level12. Therefore, an intervention that successfully reduces disparities in HCC outcomes should have these characteristics and address both patient- and system-level SSDOH. The HCC Liver-Link intervention investigators propose to develop is designed to: a) improve patients' HCC-related disease and treatment knowledge; b) screen patients for social needs and substance use and refer to social work for linkage to local services; and c) use our multidisciplinary HCC tumor board to facilitate linkage to subspecialty HCC cancer care. Earlier portions of this research project were devoted to developing the education program component of the HCC Liver-Link intervention. This intervention, a full multi-level intervention designed to address patient- and system-level SSDOH variables and facilitate access to curative HCC therapies (liver transplantation and resection) in a cohort of Black patients with Barcelona Clinic Liver Cancer prognosis stage 0, A and downstaged B disease underwent pilot testing in a previous project. The aims of this portion of the study are to estimate the effect of the HCC Liver-Link intervention on the time to receipt of curative therapies and HCC related knowledge in black patients with HCC. Toward that end, investigators will conduct a multi-center, pilot randomized controlled trial to test the multi-level intervention in 40 black BCLC 0, A or downstaged B disease patients who will be followed for 6 months or until waitlisted for liver transplant.

Eligibility Criteria

This trial is for Black patients with early-stage liver cancer (Hepatocellular Carcinoma) who have not yet received curative therapies. It aims to address racial disparities in healthcare by helping patients navigate the healthcare system and improve their knowledge about their disease and treatment options.

Inclusion Criteria

Ability to provide written informed consent and HIPAA authorization

Anyone within UCSF criteria

Self-reported Black race

Exclusion Criteria

EF<40%

I am not considered a candidate for liver surgery or transplant according to my doctor.

My BMI is over 50.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants proceed through the Liver-Link component intervention, including assessments for disease knowledge, quality of life, substance use, and social needs. They attend support groups and complete milestone checks.

6 months

3 milestone checks, 2 HCC-related visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including completion of exit surveys and knowledge assessments.

4 weeks

Treatment Details

Interventions

• Liver Link

Trial Overview The 'Liver Link' intervention is being tested to see if it can reduce the time it takes for Black patients with liver cancer to receive curative treatments. It includes education, screening for social needs and substance use, and coordination with a tumor board to connect patients to specialized care.

Participant Groups

Group I: Liver-Link Arm Experimental Treatment 1 Intervention

Those randomized to the Liver-Link portion of the study will proceed through the Liver-Link component intervention. Participation in this study will last 6 months. Participants in this group are assessed for knowledge of their disease, quality of life, substance use, and for social needs at the beginning of the program. Those who screen positive for social needs or high-risk alcohol will see social work. Participants will attend 3 support groups and compelte exit surveys. Participants will have 3 milestone checks during the 6 month study period and will be referred back to social work if they do not meet milestones. Participants will also have a knowledge assessment after a total of 2 HCC-related visits.

Group II: Standard of Care Arm Active Control 1 Intervention

Individuals in the standard of care portion of the study will complete several questionnaires at the enrollment visit . Over the duration of study participation (6 months), participants in this arm may meet with a social worker as part of their standard health care treatment and will receive education via these standard of care visits. After at least two visits related to HCC clinical care, and participants in this arm will be contacted and will be asked to complete the knowledge assessment tool. At tne end of study they will complete exit survieys via redcap or phone.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute on Minority Health and Health Disparities (NIMHD)

Collaborator

Trials

473

Recruited

1,374,000+

Findings from Research

The FDA's guidance on evaluating drug-induced liver injury (DILI) is effective for most low-risk populations but presents challenges for patients with existing liver diseases, such as viral hepatitis or cancer.

There is a pressing need for clearer guidelines and consensus on liver safety assessments, particularly regarding stopping rules based on ALT levels, to facilitate the approval and use of new antiviral and cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver safety assessment in special populations (hepatitis B, C, and oncology trials). Kullak-Ublick, GA., Merz, M., Griffel, L., et al.[2022]

In a review of 1670 patients from phase 1 oncology trials, only 4.9% developed drug-induced liver injury (DILI), indicating that while DILI can occur, it is relatively uncommon and often resolves with supportive care.

Rechallenging patients with a history of DILI carries a 28% risk of recurrence, particularly associated with higher peak alanine aminotransferase levels during the initial episode, suggesting careful consideration of treatment options is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implications of drug-induced liver injury in early-phase oncology clinical trials. Mondaca, SP., Liu, D., Flynn, JR., et al.[2022]

The study identified 504 cases of drug-induced liver injury (DILI) associated with antibody-drug conjugates (ADCs) from the FAERS database, indicating a potential safety concern with these treatments.

Specific ADCs, including trastuzumab emtansine and enfortumab vedotin, were linked to DILI, suggesting the need for further research to understand the mechanisms and develop preventive strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacovigilance study on drug-induced liver injury associated with antibody-drug conjugates (ADCs) based on the food and drug administration adverse event reporting system. Sun, C., Yang, X., Tang, L., et al.[2023]

References

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

Liver safety assessment in special populations (hepatitis B, C, and oncology trials). [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapies for advanced hepatocellular carcinoma. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor. [2020]

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

Clinical implications of drug-induced liver injury in early-phase oncology clinical trials. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A pharmacovigilance study on drug-induced liver injury associated with antibody-drug conjugates (ADCs) based on the food and drug administration adverse event reporting system. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Application of traditional Chinese medicine injection in treatment of primary liver cancer: a review. [2019]

7. China pubmed.ncbi.nlm.nih.gov

[Surgery for patients with primary liver cancer: report of 1,038 patients]. [2006]

8. Japan pubmed.ncbi.nlm.nih.gov

Extra vascular interventional treatment of liver cancer, present and future. [2015]

9. China pubmed.ncbi.nlm.nih.gov

[Results of multimodality therapy for unresectable primary liver cancer]. [2007]

10. Singapore pubmed.ncbi.nlm.nih.gov

Serial therapies oriented by surgery for large primary liver carcinoma. [2004]