Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Chlorotrianisene

Tremelimumab

Antineoplastic Agents, Immunological

1500 mg Durvalumab C1D1 + Q4W (max. 13 cycles)

Locoregional therapy will be performed as a standard-of-care procedure

Y-90 SIRT

DEB-TACE

Arndt Vogel, Prof. Dr.

Johanna Riedel, Dr.

Maria Gonzalez-Carmona, PD Dr.

Hartmut Schmidt, Prof.Dr.

Michael Schultheiss, Dr.

Udo Lindig, Dr.

Dirk Waldschmidt, Dr.

Jens Marquardt, Prof. Dr.

Ursula Ehmer, PD Dr.

Martin Fuchs, Dr.

Salah-Eddin Al-Batran, Prof. Dr.

A Phase II study of immunotherapy with Durvalumab (MEDI4736) and Tremelimumab in combination with either Y-90 SIRT or DEB-TACE for intermediate stage HCC with pick-the-winner design

The IMMUWIN phase II will test the safety and anti-tumor efficacy of the combination of Durvalumab and Tremelimumab with either Y-90 SIRT or DEB-TACE. Patients will be randomized into two experimental arms, one receiving SIRT + Durvalumab + Tremelimumab, the other arm receiving TACE + Durvalumab + Tremelimumab. It will be determined whether the combination of immunotherapy with SIRT or TACE is more promising.

Durvalumab and Tremelimumab in Combination With Either Y-90 SIRT or DEB-TACE for Intermediate Stage HCC

A Phase II Study of Immunotherapy With Durvalumab (MEDI4736) and Tremelimumab in Combination With Either Y-90 SIRT or TACE for Intermediate Stage HCC With Pick-the-winner Design

Exploratory: Correlation analysis between selected molecular parameters and clinical data to identify molecular biomarkers predictive for outcome are not fully defined at the time this protocol is written. The optional translational research program will consider the latest research data available at the time of analysis. Analysis might comprise (but is not limited to) staining for PD-L1 protein expression on tumor cells using the commercially available IVD Kits (22C3 pharmDx assay, DAKO North America) and lymphocytes, testing for expression of PD-1, PD-L1 and PD-L2, Immune cell infiltrates (IGHM, CD3, CD8, FOXP3, CD68, CD205), Chemokines (CXCL9. CXCL10, CXCL13) and invasion markers (MMP7, MMP9) and assessing circulating nucleic acids and tumor specific transcripts.

Proportion of allocated subjects with best response of complete or partial response

Time from the date of randomization to the date of first observed disease progression (investigator assessment according to RECIST 1.1) or death from any cause.

Overall survival will be determined as time from the date of treatment allocation to the date of death.

Treatment related serious adverse events rate (SAE) will be determined. All observed toxicities and side effects will be graded according to NCI CTCAE v5.0 for all patients and the degree of association of each with the study treatment assessed and summarized.

ORR as BOR during therapy will be defined as the proportion of allocated subjects with best response of complete or partial response from date of randomization until disease progression or death from any cause occurs.

ORR at 6 months for patients who received single treatment of TACE/SIRT

Quality of life will be assessed by the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30 questionnaire) and will be evaluated based on the EORTC QLQ-C30 scoring manual in its most current version at time of data analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Durvalumab and Tremelimumab in Combination With Either Y-90 SIRT or DEB-TACE for Intermediate Stage HCC	NCT04522544	Hepatocellular ... HCC	Tremelimumab Durvalumab Y-90 SIRT DEB-TACE	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Durvalumab and Tremelimumab in Combination With Either Y-90 SIRT or DEB-TACE for Intermediate Stage HCC	NCT04522544	Hepatocellular ... HCC	Tremelimumab Durvalumab Y-90 SIRT DEB-TACE	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Spots Global Cancer Trial Database for intermediate stage hcc