Immunotherapy for Liver Cancer
Recruiting in Palo Alto (17 mi)
+5 other locations
Overseen byMehmet Akce
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Academic and Community Cancer Research United
Must not be taking: Immunosuppressants, Antiretrovirals
Disqualifiers: Pregnancy, Major surgery, Autoimmune disorders, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests if two drugs, nivolumab and ipilimumab, can shrink tumors in patients with advanced liver cancer who haven't responded to other treatments. These drugs help the immune system attack and kill cancer cells.
Will I have to stop taking my current medications?
The trial requires a washout period of at least 4 weeks since the last dose of atezolizumab and bevacizumab. It does not specify other medications, so you should discuss your current medications with the study team to see if any adjustments are needed.
What data supports the effectiveness of the drug combination of Ipilimumab, Yervoy, Nivolumab, and Opdivo for liver cancer?
Research shows that combining nivolumab with ipilimumab can improve outcomes for patients with advanced liver cancer, as seen in the CheckMate 040 trial. Additionally, nivolumab alone has been associated with increased survival and manageable safety in liver cancer patients.
12345Is immunotherapy for liver cancer generally safe for humans?
Immunotherapy drugs like Ipilimumab and Nivolumab have been used for various cancers and are generally considered safe, but they can cause side effects. Common side effects include skin issues, inflammation of the colon, liver, and hormone glands, and in rare cases, severe immune-related reactions that can affect different organs.
678910How is the drug combination of ipilimumab and nivolumab unique for treating liver cancer?
The combination of ipilimumab and nivolumab is unique for treating liver cancer because it targets immune checkpoints to boost the body's immune response against cancer cells, especially after other immune therapies have failed. This approach is different from traditional treatments as it uses the body's own immune system to fight the cancer.
1112131415Eligibility Criteria
Adults with advanced liver cancer that has spread or can't be surgically removed, who have previously been treated with Atezolizumab + Bevacizumab and need a new treatment. They must meet specific health criteria like certain blood cell counts and liver function tests, not be pregnant or breastfeeding, use contraception if of childbearing potential, and cannot have had major surgery or other treatments recently.Inclusion Criteria
Willing to provide mandatory tissue specimens and blood specimens for correlative research purposes
Absolute neutrophil count (ANC) >= 1000/mm ^ 3 (obtained =< 28 days prior to registration)
Total bilirubin =< 3 x upper limit of normal (ULN) (obtained =< 28 days prior to registration)
+16 more
Exclusion Criteria
I have had cancer spread to the lining of my brain and spinal cord.
Nursing persons
I have not had a heart attack in the last 6 months and don't need ongoing therapy for severe heart rhythm problems.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive nivolumab and ipilimumab intravenously. Treatment repeats every 21 days for 4 cycles, followed by nivolumab every 28 days for up to 24 cycles.
Up to 18 months
1 visit every 21 days for 4 cycles, then 1 visit every 28 days for up to 24 cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
Up to 2 years
1 visit at 30 days post-treatment, then every 3 months
Participant Groups
The trial is testing the combination of two immunotherapy drugs called Nivolumab and Ipilimumab to see if they can shrink tumors in patients with advanced liver cancer. These drugs may help the immune system fight the cancer more effectively.
1Treatment groups
Experimental Treatment
Group I: Treatment (nivolumab, ipilimumab)Experimental Treatment2 Interventions
Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Ipilimumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Yervoy for:
- Advanced melanoma
- Stage III unresectable melanoma
- Stage IV metastatic melanoma
🇪🇺 Approved in European Union as Yervoy for:
- Advanced melanoma
- Stage III unresectable melanoma
- Stage IV metastatic melanoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory University Hospital/Winship Cancer InstituteAtlanta, GA
University of Alabama- BirminghamBirmingham, AL
Vanderbilt University/Ingram Cancer CenterNashville, TN
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, FL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Academic and Community Cancer Research UnitedLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma. [2022]To evaluate efficacy and safety of anti-PD1 therapy with nivolumab for treatment of advanced hepatocellular carcinoma (HCC).
Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial. [2022]Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy.
Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. [2022]Nivolumab, a programmed death (PD)-1 (PD-1) inhibitor, led to durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). In our retrospective analysis, we studied the immunobiology and potential associations between biomarkers and outcomes with nivolumab in HCC.
Nivolumab Plus Cabozantinib With or Without Ipilimumab for Advanced Hepatocellular Carcinoma: Results From Cohort 6 of the CheckMate 040 Trial. [2023]To investigate the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma.
Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]Frontline treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) induced durable and long-term efficacy, compared with chemotherapy, in patients with advanced non-small cell lung cancer (NSCLC) and tumor PD-L1 expression greater than 1% or less than 1%, according to updated results from part 1 of the phase 3 CheckMate 227 (NCT02477826)trial presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.
Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. [2021]Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancers. We aimed to evaluate the incidence and prognostic impact of hepatic adverse events (AEs) in a territory-wide cohort of patients who received ICIs.
Safety in treatment of hepatocellular carcinoma with immune checkpoint inhibitors as compared to melanoma and non-small cell lung cancer. [2018]Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity.
Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]To provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italian spontaneous adverse drug reaction (ADR) reporting system.
A case report of orbital inflammatory syndrome secondary to ipilimumab. [2018]Ipilimumab is a monoclonal antibody to cytotoxic T-lymphocyte antigen-4, a negative regulator of T-cell-mediated immune response. Ipilimumab is approved by the US Food and Drug Administration for the treatment of advanced melanoma. However, its use frequently has been associated with immune-related side effects, which can be explained by its mechanism of action. More common adverse effects include dermatitis, colitis, hepatitis, and endocrinopathies, but many less common immune-related adverse effects that involve various tissues and organ systems have been reported with more widespread use of ipilimumab since its approval in 2011. A case of bilateral orbital inflammatory syndrome secondary to ipilimumab, in a patient undergoing adjuvant treatment for metastatic melanoma, is reported.
Pathological characterization of nivolumab-related liver injury in a patient with glioblastoma. [2018]Immune checkpoint inhibitors such as anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies have dramatically changed the paradigm of cancer therapy over the past few years. The use of these agents is associated with a unique pattern of autoimmune-like/inflammatory side effects termed immune-related adverse events (irAEs), that may cause collateral damage to normal tissues. Although severe irAEs remain rare, they can become life-threatening if not anticipated and managed appropriately. Improving our knowledge of the mechanisms underlying the development of these toxicities is crucial to optimize clinical efficacy and safety of these new immunotherapeutics. Herein we describe for the first time the pathological features of a severe liver-injury associated with the administration of the anti-PD-1 agent nivolumab in a patient with glioblastoma.
Ipilimumab and nivolumab in advanced hepatocellular carcinoma after failure of prior immune checkpoint inhibitor-based combination therapies: a multicenter retrospective study. [2023]Immune checkpoint inhibitor (ICI)-based regimens are transforming the landscape of hepatocellular carcinoma (HCC) treatment. We describe the effect of combined ipilimumab and nivolumab in patients with advanced HCC after the failure of prior ICI-based combination treatments.
Ipilimumab: first global approval. [2021]Ipilimumab (Yervoy®) is an anti-cytotoxic T-lymphocyte antigen (CTLA)-4 monoclonal antibody that has been approved in the US for the first- or second-line treatment of patients with malignant melanoma. In the EU, it is awaiting approval as second-line therapy for melanoma. Ipilimumab blocks the effects of the negative T-cell regulator CTLA-4, which may in turn augment T-cell responses to tumour cells. Preclinical studies have indicated that antibody blocking of CTLA-4 can lead to potent immune responses. Ipilimumab is also in development as first- and second-line therapy for prostate cancer where it has progressed to phase III clinical trials worldwide, and it is in phase II development for non-small cell lung cancer. Ipilimumab was originated by the University of California, Berkeley, in the US and subsequently licensed to Medarex, which was later acquired by Bristol-Myers Squibb. This article summarizes the milestones in the development of intravenous ipilimumab leading to this first approval. This profile has been extracted from Wolters Kluwer's R&D Insight drug pipeline database. R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.
Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.
Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. [2022]Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis.
Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors. [2022]Programmed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.