Hepatocellular Carcinoma (HCC)
Conditions
Keywords
HCC, TIPS, Tecentriq, Avastin, transjugular intrahepatic portosystemic shunting, Hepatocellular carcinoma, observational study, non-interventional study, Atezolizumab, Bevacizumab
Brief summary
The NISTIPS TRITICC-4 study is a prospective, multicentre, non-interventional cohort study to analyze the effectiveness of transjugular intrahepatic portosystemic shunting (TIPS) in patients with Hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab as first-line treatment. It will further characterize the effectiveness of atezolizumab and bevacizumab therapy, investigate post-market safety and evaluate health-related quality in HCC patient cohorts with or without TIPS in a real-world setting.
Detailed description
While TIPS effectively treats CSPH in cirrhosis, its role in HCC patients receiving systemic therapy remains unclear. The NISTIPS TRITICC-4 study will investigate whether TIPS in patients receiving atezo+bev reduces portal hypertension-related complications and improves therapy outcomes. We hypothesize that TIPS is feasible in non-resectable HCC, lowers the risk of hepatic decompensation, and improves survival and treatment effectiveness by preserving liver function. Furthermore, an observational cohort study like NISTIPS TRITICC-4 offers an opportunity to evaluate the effectiveness, safety and tolerability of atezo+bev treatment with or without TIPS in a more heterogeneous patient population, by capturing data on treatment outcomes, quality of life, and safety in daily clinical practice. Moreover, it helps to identify patient subgroups, which may derive benefits or experience specific risks, helping to optimize personalized treatment strategies. The NISTIPS TRITICC-4 study is a prospective, multicentre, cohort study with associated accompanying research including archival tissue sample collection, which enrolls 350 patients in Germany of both sexes and ages over 18 years. Eligible patients are diagnosed with locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) in 1st line therapy setting without (Analysis Cohort 1) or with (Analysis Cohort 2) TIPS receiving atezolizumab + bevacizumab according to the market authorization.
Interventions
None listed
Sponsors
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Roche Pharma AG
Heinrich-Heine University, Duesseldorf
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient has a histologically confirmed, locally advanced or metastatic and/or unresectable HCC with: 1. the presence of liver cirrhosis (cirrhosis confirmed by histology or liver stiffness or with unequivocal signs in ultrasound, endoscopy, and/or blood tests), 2. a disease that is not amenable to curative surgical and/or locoregional therapies, or a progressive disease after surgical and /or locoregional therapies, 2. A decision for treatment with atezolizumab + bevacizumab according to the market authorization with or without TIPS has been made before enrolling into the study by the treating physician. NOTE: Patients who have already received 1-2 cycles of atezo+bev therapy are eligible for enrollment into the NISTIPS TRITICC-4 study, when the prescription of the medicine or other therapeutic strategies are clearly separated from the decision to include the patient in the study.
Exclusion criteria
1. The patient has not provided signed informed consent. 2. The patient is under 18 years of age at the time of giving signed informed consent. 3. The patient is unable to understand all implications of study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to deterioration of liver function (TTDL) | up to 72 months | Time to deterioration of liver function (TTDL) is used as outcome measure to analyze the effectiveness of transjugular intrahepatic portosystemic shunting (TIPS) in patients with Hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab as first-line treatment in a real-world scenario. Liver function deterioration is registered if any of the following criteria was met for more than 4 weeks (\>28 days in a row): * Total bilirubin \> 2.0 x ULN OR \> 2.0 x baseline if baseline was abnormal * Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) \> 5x ULN OR \> 5.0 x baseline if baseline was abnormal * Alkaline phosphatase \>2.5x ULN OR \> 2.5 x baseline (if baseline was abnormal) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | up to 72 months | Overall survival (OS) is used as measurement to further characterize the effectiveness of atezolizumab and bevacizumab therapy in real-world HCC patient cohorts with or without TIPS. |
| Time on treatment (ToT) | up to 72 months | Time on treatment (ToT), defined as duration from the first day of atezo+bev therapy to the day of the last dose of atezo+bev therapy |
| Prevalence of bleeding adverse events | up to 72 months | Prevalence of bleeding adverse events post-administration of atezo+bev treatment |
| Overall Response Rate (ORR) | up to 72 months | Overall Response Rate (ORR) defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), as assessed by the investigator according to local protocol. |
| Time to New Extrahepatic Lesions or death due to any cause (TTNEL) | up to 72 months | Time to New Extrahepatic Lesions or death due to any cause (TTNEL) after initiation of atezo+bev treatment |
| Post-market safety of atezolizumab plus bevacizumab | up to 72 months | To investigate post-market safety of the authorized treatment with atezolizumab plus bevacizumab in HCC patient cohorts with or without TIPS, type, frequency, causality and severity of adverse events with severity according to NCI CTCAE v5.0 including the rate of TIPS-related complications will be analyzed. |
| Proportion of patients with improved, maintained, or worsened Health-Related Quality of Life (HR-QoL) according to EORTC QLQ-C30 and QLQ-HCC18 assessment | up to 72 months | Proportion of patients with improved, maintained, or worsened Health-Related Quality of Life (HR-QoL) scores with a ≥ 10-point change considered clinically meaningful in HR-QoL scores derived from EORTC QLQ-C30 and QLQ-HCC18 assessment is the used measurement to evaluate health-related quality of life in real-world HCC patient cohorts receiving atezolizumab plus bevacizumab as first-line treatment with or without TIPS. |
| Time to HR-QoL Deterioration (HR-QoL TTD) derived from EORTC QLQ-C30 and QLQ-HCC18 assessment | up to 72 months | Time to HR-QoL Deterioration (HR-QoL TTD), measured from study enrolment to the first ≥10 points decrease of HR-QoL score compared to baseline HR-QoL score with HR-QoL scores derived from EORTC QLQ-C30 and QLQ-HCC18 assessment, is the used measurement to evaluate health-related quality of life in real-world HCC patient cohorts receiving atezolizumab plus bevacizumab as first-line treatment with or without TIPS. |
Countries
Germany
Contacts
CONTACTChristoph Roderburg, Professor
CONTACTBianca Zaepf
PRINCIPAL_INVESTIGATORChristoph Roderburg, Professor
Heinrich Heine University of Duesseldorf, University Hospital of Duesseldorf
Outcome results
None listed