Nivolumab + deb-TACE for Liver Cancer

Recruiting at 8 trial locations

Overseen By James Harding, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HIV/AIDS, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 28

Duration: 52 weeks

20 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you must stop them 14 days before starting the study drug, unless they are inhaled or topical steroids, or low-dose adrenal replacement.

What data supports the effectiveness of the treatment Nivolumab + deb-TACE for Liver Cancer?

Research shows that drug-eluting bead transarterial chemoembolization (DEB-TACE) is effective in treating liver cancer, with a good response rate compared to conventional methods. Additionally, combining DEB-TACE with immune therapies like PD-1 inhibitors has shown promising results in improving treatment outcomes for liver cancer. ^{1 2 3 4 5}

Is the combination of Nivolumab and deb-TACE safe for liver cancer treatment?

Nivolumab, used in liver cancer treatment, has been studied for safety, showing some treatment-related side effects like liver issues. It can also cause hepatitis B reactivation, which might lead to treatment delays or changes. Overall, while it has shown safety in various cancers, monitoring for liver-related side effects is important. ^{6 7 8 9 10}

How is the treatment Nivolumab + deb-TACE for liver cancer different from other treatments?

This treatment combines Nivolumab, an immune therapy that helps the body's immune system attack cancer cells, with drug-eluting bead transarterial chemoembolization (DEB-TACE), which delivers chemotherapy directly to the liver tumor, reducing side effects compared to traditional methods. This combination is unique because it targets the cancer both by boosting the immune response and by directly attacking the tumor with localized chemotherapy. ^{2 3 4 5 11}

What is the purpose of this trial?

The purpose of the study is to find out the effects of using nivolumab with Drug Eluting Bead Transarterial Chemoembolization (deb-TACE) in the treatment of liver cancer.

Research Team

James Harding, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with confirmed liver cancer (HCC) that can't be removed by surgery or treated with a transplant. They should have measurable disease, be in good physical condition (ECOG 0 or 1), and have well-functioning bone marrow, liver, and kidneys. People with prior liver transplants, certain other cancers, severe allergies to contrast agents used in scans, HIV/AIDS, active autoimmune diseases (with some exceptions), or on high-dose steroids are excluded.

Inclusion Criteria

My liver, kidneys, and bone marrow are functioning well.

Albumin ≥ 2.8 g/dL

My liver cancer cannot be cured with surgery, but it can be treated with a specific procedure.

Exclusion Criteria

I cannot undergo angiography/embolization due to medical reasons.

You have had a serious allergic reaction to contrast dye in the past, even with medication to prevent it.

Women of childbearing potential (WOCBP) or sexually active men must use appropriate method(s) of contraception.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive nivolumab every two weeks starting 4 weeks prior to deb-TACE

4 weeks

2 visits (in-person)

Treatment

Participants undergo deb-TACE and continue nivolumab every two weeks for up to one year

52 weeks

26 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Drug Eluting Bead Transarterial Chemoembolization
• Nivolumab

Trial Overview The trial is testing the combination of nivolumab (an immunotherapy drug) with deb-TACE—a procedure where chemotherapy drugs are delivered directly to the liver tumor through blood vessels—to see if it's safe and works for treating liver cancer.

Participant Groups

Group I: Cohort 3, deb-TACE + Nivolumab Experimental Treatment 2 Interventions

3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Nivolumab will be dosed every two weeks starting 4 weeks prior to deb-TACE (Week 4) and continue every 2 weeks for up to one year. If no participants experience a DLT in the initial group of 3 participants, an additional 3 participants will be added to confirm safety. If less than or equal to 1 of 6 participants experiences a DLT, this will be considered the optimal schedule.

Group II: Cohort 2, deb-TACE + Nivolumab Experimental Treatment 2 Interventions

3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Participants will receive nivolumab every two weeks for up to one year, starting 4 weeks prior to deb-TACE (week -4). Participants in this cohort will not receive nivolumab on the day of deb-TACE. If no participants experience a DLT in the initial group of 3 participants or if 1 of 6 participants experiences a DLT, a new group of participants will be enrolled into Cohort 3.

Group III: Cohort 1, deb-TACE + Nivolumab Experimental Treatment 2 Interventions

3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Two weeks after deb-TACE, participants will begin nivolumab every two weeks for up to one year. If no participants experience a dose limiting toxicity (DLT), or 1 of 6 participants experiences a DLT, a new group of participants will be enrolled into Cohort 2.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Nivolumab has a manageable safety profile in patients with advanced hepatocellular carcinoma (HCC), with 68% of select treatment-related adverse events (sTRAEs) resolving after treatment, indicating it can be a viable option for this patient group.

The most common sTRAEs were skin-related (35.5%), with gastrointestinal and hepatic events occurring in about 14% of patients, mostly at grade 1/2 severity, suggesting that early management and patient education on monitoring for these events are crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study. Julien, K., Leung, HT., Fuertes, C., et al.[2022]

In a study of 1480 cancer patients treated with immune checkpoint inhibitors (ICIs), over 50% experienced hepatic adverse events (AEs), with 14.9% classified as severe (grade 3-4).

The presence of hepatic AEs was linked to poorer overall survival rates, with median survival dropping from 9.0 months for patients without AEs to just 3.3 months for those with severe hepatic AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. Chan, SL., Yip, TC., Wong, VW., et al.[2021]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

A meta-analysis of nine randomized controlled trials showed that PD-1 inhibitors significantly increase the risk of developing all-grade hepatic adverse events (AEs) in cancer patients, although high-grade AEs were not significantly affected compared to chemotherapy or everolimus.

The combination of nivolumab and ipilimumab resulted in a notably higher risk of all-grade and high-grade hepatic AEs compared to ipilimumab alone, indicating that while PD-1 inhibitors can be effective, they also carry a risk of liver-related side effects, primarily of lower severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis. Zhang, X., Ran, Y., Wang, K., et al.[2018]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Comparison of doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma]. [2016]

2. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of the Combination of Transarterial Chemoembolization with Camrelizumab plus Apatinib for Advanced Hepatocellular Carcinoma: A Retrospective Study of 38 Patients from a Single Center. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study. [2020]

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

Initial Experience of Drug-Eluting Bead-Transcatheter Arterial Chemoembolization After Lipiodol-Based Transcatheter Arterial Chemoembolization Failure for Patients with Advanced Hepatocellular Carcinoma. [2022]

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

Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Lenvatinib and Anti-PD-1 Antibodies for Unresectable Hepatocellular Carcinoma: A Retrospective Analysis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study. [2022]

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

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. [2021]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

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

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis. [2018]

10. China pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. [2022]

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

Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma. [2020]