Hepatocellular carcinoma MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Clínica Universidad de Navarra/Universidad de Navarra
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 18-years-old or above Diagnosis of HCC based on histology or non-invasive criteria if cirrhotics. Patients with fibrolamellar carcinoma are not excluded. Chronic liver disease absent, non-viral or due to hepatitis C or B virus infection. Subjects with chronic HBV infection must be on effective antiviral therapy Preserved liver function (without cirrhosis or with compensated cirrhosis in Child Pugh Class A). ECOG performance status 0 or 1 Willing to have a liver biopsy pre-treatment Considered candidates for locoregional therapy using SIR-Spheres based on • the absence of extrahepatic disease. • unsuitability for liver resection or transplantation, or percutaneous ablation • considered not good candidates for TACE because they have: o Single tumors larger than 5 cm. Unsuitability for TACE in patients with single tumors of size between 5 and 10 cm will follow local practice in the treating center. o Multiple tumors that cannot be targeted superselectively. These patients should be in the BCLC-B2 substage proposed by Bolondi et al (3). In summary, they should fall within the up-to-7 rule (the sum of the number of tumors and the maximal size of the largest lesion in cm should be higher than 7) and should be in a Child-Pugh stage A. Unsuitability for TACE in patients with multiple tumors within the BCLC-B2 substage will follow local practice in the treating center. o Unilobar tumors with segmental or lobar portal vein thrombosis. Patients that have a small burden of disease (40 mL/min. • AST and ALT = 5 X ULN • Bilirubin = 2 mg/dL • INR = 1.8. • Albumin = 2.8 g/dL Willing and able to comply with immune-monitoring sample collection and required study follow-up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Any history of hepatic encephalopathy Any prior (within 1 year) or current clinically significant ascites. Any history of clinically meaningful variceal bleeding within the last three months. Active coinfection with both hepatitis B and C or hepatitis D infection in subjects with hepatitis B Occlusive main trunk portal vein thrombosis or absence of intrahepatic portal blood flow if patient carries a portocaval shunt. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured. Any active autoimmune disease. Any severe organ disease Prior therapy with any drug specifically targeting T-cell costimulation or checkpoint pathways. Prior organ allograft or allogeneic bone marrow transplantation Recent active bacterial or fungal infections. Any condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety of nivolumab in combination with SIRT using SIR-Spheres;Secondary Objective: The secondary objective is to evaluate the antitumoral activity of nivolumab in combination with SIRT using SIR-Spheres. Exploratory objectives are: • To evaluate the role of tissue biomarkers (tumor immune cell infiltrate, PD-1 and PD-L1 expression, peripheral blood markers) in determining the antitumoral activity of nivolumab in combination with SIRT using SIR-Spheres. • To evaluate the utility of baseline or on-treatment variables that may serve as surrogate markers of efficacy.;Primary end point(s): The primary endpoint is the rate and type of adverse events (AEs), serious AEs, liver decompensation, and transient and permanent drug discontinuations due to toxicity;Timepoint(s) of evaluation of this end point: Up to 100 days after the last dose of nivolumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are the rate of objective response, disease control, duration of response and time to progression based on RECIST criteria v 1.1, as well as the pattern of progression and overall survival (OS). Exploratory endpoints are: • PD-1 and PD-L1 expression in tumor samples, TILs density, inflammatory blood markers. • ALBI score at baseline and time to progression untreatable by locoregional therapies.;Timepoint(s) of evaluation of this end point: For the entire duration of the study | — |
Countries
Spain
Contacts
Public ContactUCEC
Clinica Universidad de Navarra
Outcome results
None listed