Clinical trial • Phase III • Oncology

DURVALUMAB for Hepatocellular carcinoma (advanced)

Phase III trial of DURVALUMAB for Hepatocellular carcinoma (advanced).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Hepatocellular carcinoma (advanced)
Trial Stage
Phase III
Drug Modality
Monoclonal antibody | Small molecule

Key dates

Initial CTIS Submission Date
18-06-2024
First CTIS Authorization Date
12-07-2024

Trial design

Randomised, open-label, arm d: sorafenib 400 mg bid therapy; other arms: arm a durvalumab 1500 mg monotherapy; arm b durvalumab 1500 mg + tremelimumab 75 mg ×4 doses; arm c durvalumab 1500 mg + tremelimumab 300 mg ×1 dose.-controlled Phase III trial across 26 sites in Italy, Spain, Germany and others.

Randomised
Yes
Open Label
Yes
Comparator
Arm D: Sorafenib 400 mg BID therapy; Other arms: Arm A Durvalumab 1500 mg monotherapy; Arm B Durvalumab 1500 mg + Tremelimumab 75 mg ×4 doses; Arm C Durvalumab 1500 mg + Tremelimumab 300 mg ×1 dose.
Biomarker Stratified
True, PD-L1 expression (strata not specified)
Target Sample Size
1302

Eligibility

Recruits 1302 adults.

Inclusion criteria

  • {"criterion_text":"- HCC based on histopathological confirmation"}
  • {"criterion_text":"- No prior systemic therapy for HCC"}
  • {"criterion_text":"- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C"}
  • {"criterion_text":"- Child-Pugh Score class A"}
  • {"criterion_text":"- ECOG performance status of 0 or 1 at enrollment"}

Exclusion criteria

  • {"criterion_text":"- Hepatic encephalopathy within past 12 months or requirement for medication to prevent or control encephalopathy"}
  • {"criterion_text":"-\tClinical meaningful ascites"}
  • {"criterion_text":"-\tMain portal vein thrombosis"}
  • {"criterion_text":"-\tActive or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months"}
  • {"criterion_text":"-\tHBV and HVC coinfection, or HBV and Hep D coinfection"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Overall survival (OS) is defined as the time from the date of randomization until death due to any cause.","definition_or_measurement_approach":"Time from the date of randomization until death due to any cause."}

Secondary endpoints

  • {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Time to progression (TTP)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Disease control rate (DCR)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":""}

Other endpoints

  • {"endpoint_text":"- To assess the efficacy of durvalumab monotherapy compared with sorafenib","definition_or_measurement_approach":""}
  • {"endpoint_text":"- To assess the safety and tolerability profile across all treatment arms","definition_or_measurement_approach":""}
  • {"endpoint_text":"- To assess the efficacy of durvalumab monotheraphy and durvalumab plus tremelimumab combination theraphy compared with sorafenib by PD-L1 expression","definition_or_measurement_approach":""}
  • {"endpoint_text":"- To assess disease-related symptoms, impacts, and health-related quality of life (HRQoL) in durvalumab monotheraphy and durvalumab plus tremelimimab combination therapy compared with sorafenib","definition_or_measurement_approach":""}
  • {"endpoint_text":"- To evaluate the population PK and pharmacodynamics of durvalumab monotheraphy and durvalumab plus tremelimumab combination therapy","definition_or_measurement_approach":""}
  • {"endpoint_text":"- To investigate the immunogenicity of durvalumab monotheraphy and durvalumab plus tremelimumab combination therapy","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
1302
Recruitment Window Months
6

Geography

Total Number Of Sites
26
Total Number Of Participants
302

Italy

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
29-08-2025
Processing Time Days
427
Number Of Sites
5
Number Of Participants
77

Sites

Site Name
Azienda Ospedaliera “G. Rummo”
Department Name
U.O.C. ONCOLOGIA MEDICA
Principal Investigator Name
Domenico Germano
Principal Investigator Email
domgerm@libero.it
Contact Person Name
Domenico Germano
Contact Person Email
domgerm@libero.it
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
U. O. ONCOLOGIA MEDICA
Principal Investigator Name
Gianluca Masi
Principal Investigator Email
gianluca.masi@unipi.it
Contact Person Name
Gianluca Masi
Contact Person Email
gianluca.masi@unipi.it
Site Name
Humanitas Mirasole S.p.A.
Department Name
U.O.DI ONCOLOGIA MEDICA ED EMATOLOGIA
Principal Investigator Name
Lorenza Rimassa
Principal Investigator Email
lorenza.rimassa@cancercenter.humanitas.it
Contact Person Name
Lorenza Rimassa
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Dipartimento di Medicina e chirurgia traslazionale
Principal Investigator Name
Antonio Gasbarrini
Principal Investigator Email
antonio.gasbarrini@unicatt.it
Contact Person Name
Antonio Gasbarrini
Contact Person Email
antonio.gasbarrini@unicatt.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
U.O. Oncologia Medica
Principal Investigator Name
Monica Ronzoni
Principal Investigator Email
ronzoni.monica@hsr.it
Contact Person Name
Monica Ronzoni
Contact Person Email
ronzoni.monica@hsr.it

Spain

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
04-08-2025
Processing Time Days
402
Number Of Sites
4
Number Of Participants
42

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Unidad de Hepatología
Principal Investigator Name
Jorge Adeva Alfonso
Principal Investigator Email
jorge.adeva@salud.madrid.org
Contact Person Name
Jorge Adeva Alfonso
Contact Person Email
jorge.adeva@salud.madrid.org
Site Name
Hospital Universitario Central De Asturias
Department Name
Unidad de Hepatología
Principal Investigator Name
Maria Varela Calvo
Principal Investigator Email
maria.varela.calvo@gmail.com
Contact Person Name
Maria Varela Calvo
Contact Person Email
maria.varela.calvo@gmail.com
Site Name
Clinica Universidad De Navarra
Department Name
Unidad de Hepatología
Principal Investigator Name
Bruno Sangro
Principal Investigator Email
bsangro@unav.es
Contact Person Name
Bruno Sangro
Contact Person Email
bsangro@unav.es
Site Name
Hospital Clinic De Barcelona
Department Name
Unidad de Hepatología
Principal Investigator Name
Maria Elisa Reig Monzón
Principal Investigator Email
MREIG1@clinic.cat
Contact Person Name
Maria Elisa Reig Monzón
Contact Person Email
MREIG1@clinic.cat

Germany

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
02-04-2026
Processing Time Days
647
Number Of Sites
6
Number Of Participants
69

Sites

Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Gastroenterologie, Hepatologie und Endokrinologie
Principal Investigator Name
Thomas Wirth
Principal Investigator Email
wirth.thomas@mh-hannover.de
Contact Person Name
Thomas Wirth
Contact Person Email
wirth.thomas@mh-hannover.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Medizinische Klinik 2 Poliklinik Gastroenterologie
Principal Investigator Name
Alexander Philipp
Principal Investigator Email
Alexander.Philipp@med.uni-muenchen.de
Contact Person Name
Alexander Philipp
Site Name
Universitaetsklinikum Essen AöR
Department Name
Gastroenterologie und Hepatologie Medizinisches Zentrum
Principal Investigator Name
Katharina Willuweit
Principal Investigator Email
katharina.willuweit@uk-essen.de
Contact Person Name
Katharina Willuweit
Site Name
University Hospital Cologne AöR
Department Name
Klinik für Gastroenterologie und Hepatologie
Principal Investigator Name
Dirk Waldschmidt
Principal Investigator Email
dirk-thomas.waldschmidt@uk-koeln.de
Contact Person Name
Dirk Waldschmidt
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Klinik für Gastroenterologie Medizinische Klinik III
Principal Investigator Name
Marie-Luise Berres
Principal Investigator Email
mberres@ukaachen.de
Contact Person Name
Marie-Luise Berres
Contact Person Email
mberres@ukaachen.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Abteilung Innere Medizin I Hepatologie, Gastroenterologie, Infektiologie
Principal Investigator Name
Michael Bitzer
Principal Investigator Email
michael.bitzer@med.uni-tuebingen.de
Contact Person Name
Michael Bitzer

France

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
04-05-2026
Processing Time Days
311
Number Of Sites
11
Number Of Participants
114

Sites

Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Gastroenterology
Principal Investigator Name
Jean-Marc PHELIP
Principal Investigator Email
j.marc.phelip@chu-st-etienne.fr
Contact Person Name
Jean-Marc PHELIP
Site Name
CHU Hôtel Dieu
Department Name
Hepato-gastroenterology
Principal Investigator Name
Yann TOUCHEFEU
Principal Investigator Email
yann.touchefeu@chu-nantes.fr
Contact Person Name
Yann TOUCHEFEU
Contact Person Email
yann.touchefeu@chu-nantes.fr
Site Name
Institut Paoli Calmettes
Department Name
Medical oncology
Principal Investigator Name
Simon Launay
Principal Investigator Email
launays@ipc.unicancer.fr
Contact Person Name
Simon Launay
Contact Person Email
launays@ipc.unicancer.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
Medical oncology
Principal Investigator Name
Frédéric DI FIORE
Principal Investigator Email
Frederic.Di-Fiore@chu-rouen.fr
Contact Person Name
Frédéric DI FIORE
Contact Person Email
Frederic.Di-Fiore@chu-rouen.fr
Site Name
Hopital Beaujon
Department Name
Service d'Oncologie Digestive
Principal Investigator Name
Mohamed BOUATTOUR
Principal Investigator Email
mohamed.bouattour@aphp.fr
Contact Person Name
Mohamed BOUATTOUR
Contact Person Email
mohamed.bouattour@aphp.fr
Site Name
C.H.U. de Montpellier - Hopital Saint Eloi
Department Name
Medical oncology
Principal Investigator Name
Eric ASSENAT
Principal Investigator Email
celine-girard@chu-montpellier.fr
Contact Person Name
Eric ASSENAT
Site Name
CHU Toulouse Rangueil
Department Name
Digestive and Gynecological Medical Oncology
Principal Investigator Name
Jean-Marie PERON
Principal Investigator Email
peron.jm@chu-toulouse.fr
Contact Person Name
Jean-Marie PERON
Contact Person Email
peron.jm@chu-toulouse.fr
Site Name
CHRU De Nancy
Department Name
Hepato-gastroenterology
Principal Investigator Name
Jean-Pierre BRONOWICKI
Principal Investigator Email
jp.bronowicki@chru-nancy.fr
Contact Person Name
Jean-Pierre BRONOWICKI
Contact Person Email
jp.bronowicki@chru-nancy.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Hepato-gastroenterology
Principal Investigator Name
Anne-Claire FRIN
Principal Investigator Email
frin.ac@chu-nice.fr
Contact Person Name
Anne-Claire FRIN
Contact Person Email
frin.ac@chu-nice.fr
Site Name
CHU de Poitiers
Department Name
Hepato-gastroenterology
Principal Investigator Name
David TOUGERON
Principal Investigator Email
david.tougeron@chu-poitiers.fr
Contact Person Name
David TOUGERON
Contact Person Email
david.tougeron@chu-poitiers.fr
Site Name
Institut Gustave Roussy
Department Name
Medical oncology
Principal Investigator Name
Valérie BOIGE
Principal Investigator Email
valerie.boige@gustaveroussy.fr
Contact Person Name
Valérie BOIGE
Contact Person Email
valerie.boige@gustaveroussy.fr

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
IMFINZI 50 mg/mL concentrate for solution for infusion.
Active Substance
DURVALUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (EU/1/18/1322/001)
Starting Dose
1500 mg
Dose Levels
1500 mg
Maximum Dose
1500 mg
Investigational Product Name
IMJUDO 20 mg/ml concentrate for solution for infusion.
Active Substance
TREMELIMUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (EU/1/22/1713/002)
Starting Dose
75 mg (one regimen) and 300 mg (alternative single-dose regimen)
Dose Levels
75 mg ×4 doses; 300 mg ×1 dose
Maximum Dose
300 mg
Investigational Product Name
Nexavar 200 mg film-coated tablets
Active Substance
SORAFENIB
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (EU/1/06/342/001)
Starting Dose
400 mg BID (as described for Arm D)
Dose Levels
400 mg BID
Frequency
BID
Maximum Dose
400 mg BID
Investigational Product Name
Mycophenolate Mofetil 500 mg film-coated tablets
Active Substance
MYCOPHENOLATE MOFETIL
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (PL 20117/0065)
Investigational Product Name
Inflectra 100 mg powder for concentrate for solution for infusion
Active Substance
INFLIXIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (EU/1/13/854/002)
Combination Treatment
Yes

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