intermediate stage hepatocellular carcinoma (HCC) MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10049010 Term: Carcinoma hepatocellular System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code
Conditions
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 2. Age = 18 years at time of study entry 3. Multinodular or large, solitary HCC, not eligible for resection or local ablation, Tumor burden below 50% of liver volume 4. Histologically confirmed diagnosis of HCC. 5. At least one measurable site of disease as defined by modified RECIST (mRECIST) criteria with spiral CT scan or MRI. 6. Child-Pugh A, Performance status (PS) = 2 (ECOG scale) 7. Subjects with chronic HBV infection must have HBV DNA viral load =65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. Diffuse HCC or presence of vascular invasion or extrahepatic spread with the following exceptions - Invasion of a segmental portal or hepatic veins - Limited extrahepatic metastases with one organ system manifestations, e.g. lymphnodal, pulmonary, ossary metastases. For lymphonodal metastases maximum three metastases, max. 2 cm in the longest diameter, and for all other metastases only solitary metastases, max. 2 cm in the longest diameter, are allowed 2. Patients on a liver transplantation list or with advanced liver disease as defined below - Encephalopathy - Untreatable ascites 3. Any contraindications for hepatic embolization procedures - Known hepatofugal blood flow - Known porto-systemic shunt - Impaired clotting test (platelet count 1.25) - Renal failure/ insufficiency requiring hemo-or peritoneal dialysis - Known severe atheromatosis - Total thrombosis or total invasion of the main branch of the portal vein 4. History of cardiac disease - Congestive heart failure > NYHA class 2 - Active coronary artery disease (myocardial infarction =6 months prior to study entry is allowed) - Cardiac arrhythmias (>Grade 2 NCI-CTCAE Version 4.03) which are poorly controlled with anti-arrhythmic therapy or requiring pace maker - Uncontrolled hypertension - Clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment (TACE + nivolumab) 5. Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein 6. Prior systemic anti-cancer therapy OR endocrine- OR immunotherapy 7. Prior treatment with TACE 8. RFA and resection administered less then 4 weeks 9. Radiotherapy administered less then 4 weeks 10. Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery 11. Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix 12. Immunocompromised patients, e.g. patients who are known HIV 13. Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer 14. Previous treatment in the present study 15. Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to - history of interstitial lung disease - HBV and HCV coinfection - known acute or chronic pancreatitis - active tuberculosis - any other active infection requiring systemic therapy - history of allogeneic tissue/solid organ transplant - diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of nivolumab-monotherapy treatment - active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents - Live vaccine within 30 days prior to the first dose of nivolumab treatment or during study treatment - History or clinical evidence of CNS metastases 16. Medication that is known to interfere with any of th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the study is the assessement of the clinical activity of the anti-programmed-death-1 antibody (anti-PD-1) nivolumab in combination with transarterial chemoembolization (TACE) in patients with multinodular, intermediate stage hepatocellular carcinoma (HCC) as first line therapy.;Secondary Objective: Secondary objectives of this study are: 1.) to assess efficacy by PFS, TTP, TTFS, duration of response and OS 2.) safety and tolerability of nivolumab in combination with TACE in patients with intermediate stage HCC. 3.) Quality of Life analysis ;Primary end point(s): ORR according to modified RECIST for HCC;Timepoint(s) of evaluation of this end point: End of study (EoS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • tumor response according to RECIST 1.1 • PFS • TTP • Time to Failure of Strategy (TTFS): - Progression according to mRECIST for HCC with the exception of new intrahepatic lesions, which are assessed to be treatable with one additional locoregional therapy (TACE, RFA/ MWA or resection). Progression following one additional locoregional treatment of such lesions according to mRECIST would be equivalent to failure of strategy. • Duration of response • Duration of treatment • OS • QoL (EORTC QLQC30 and HCC-18) • AEs/SAEs;Timepoint(s) of evaluation of this end point: End of study (EoS) | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed