This is a randomized, open-label, multi-center, global, Phase III study to assess the effectiveness and safety of two Immune Therapy drugs, durvalumab given by itself or with tremelimumab versus sorafenib, the standard first line treatment, to treat patients with no prior systemic therapy for advanced liver cancer (hepatocellular carcinoma) that cannot be removed by surgery (unresectable).

2024-512212-21-00 Protocol D419CC00002 Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 28 Nov 2017 · Status Ongoing, recruitment ended · 4 EU/EEA countries · 26 sites · Protocol D419CC00002

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 1,604
Countries 4
Sites 26

Advanced hepatocellular carcinoma (HCC)

To assess the efficacy of durvalumab plus tremelimumab combination therapy compared with sorafenib.

Key facts

Sponsor
AstraZeneca AB
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
28 Nov 2017 → ongoing
Decision date (initial)
2024-07-22
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
AstraZeneca AB

External identifiers

EU CT number
2024-512212-21-00
EudraCT number
2016-005126-11
ClinicalTrials.gov
NCT03298451

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the efficacy of durvalumab plus tremelimumab combination therapy compared with sorafenib.

Secondary objectives 1

  1. "To assess the efficacy of durvalumab monotherapy compared with sorafenib To assess the safety and tolerability profile across all treatment arms - To assess the efficacy of durvalumab monotheraphy and durvalumab plus tremelimumab combination theraphy compared with sorafenib by PD-L1 expression - 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 - To evaluate the population PK and pharmacodynamics of durvalumab monotheraphy and durvalumab plus tremelimumab combination therapy - To investigate the immunogenicity of durvalumab monotheraphy and durvalumab plus tremelimumab combination therapy"

Conditions and MedDRA coding

Advanced hepatocellular carcinoma (HCC)

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 n/a
n/a
 Randomised Controlled None Arm A: Durvalumab 1500 mg monotherapy
Arm B: Durvalumab 1500 mg plus tremelimumab 75 mg×4 doses combination therapy
Arm C: Durvalumab 1500 mg plus tremelimumab 300 mg×1 dose combination therapy
Arm D: Sorafenib 400 mg BID therapy

Regulatory references

Scientific advice from competent authorities
European Medicines Agency
Plan to share IPD
No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

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

Exclusion criteria 1

  1. Hepatic encephalopathy within past 12 months or requirement for medication to prevent or control encephalopathy - Clinical meaningful ascites - Main portal vein thrombosis - Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months - HBV and HVC coinfection, or HBV and Hep D coinfection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Overall survival (OS) is defined as the time from the date of randomization until death due to any cause.

Secondary endpoints 1

  1. Progression-free survival (PFS), Time to progression (TTP), Objective response rate (ORR), Disease control rate (DCR), and Duration of response (DoR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

IMJUDO 20 mg/ml concentrate for solution for infusion.

PRD10239823 · Product

Active substance
Tremelimumab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
300 mg milligram(s)
Max total dose
300 mg milligram(s)
Max treatment duration
9999999 Month(s)
Authorisation status
Authorised
ATC code
L01FX20 — -
Marketing authorisation
EU/1/22/1713/002
MA holder
ASTRAZENECA AB
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

IMFINZI 50 mg/mL concentrate for solution for infusion.

PRD6651398 · Product

Active substance
Durvalumab
Substance synonyms
MEDI4736
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1500 mg milligram(s)
Max total dose
1500 mg milligram(s)
Max treatment duration
9999999 Month(s)
Authorisation status
Authorised
ATC code
L01XC28 — -
Marketing authorisation
EU/1/18/1322/001
MA holder
ASTRAZENECA AB
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 1

Nexavar 200 mg film-coated tablets

PRD3117113 · Product

Active substance
Sorafenib
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
400 mg milligram(s)
Max total dose
400 mg milligram(s)
Max treatment duration
9999999 Month(s)
Authorisation status
Authorised
ATC code
L01EX02 — -
Marketing authorisation
EU/1/06/342/001
MA holder
BAYER AG
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 2

Mycophenolate Mofetil 500 mg film-coated tablets

PRD1597921 · Product

Active substance
Mycophenolate Mofetil
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
00 mg milligram(s)
Max total dose
00 mg milligram(s)
Max treatment duration
9999999 Month(s)
Authorisation status
Authorised
ATC code
L04AA06 — MYCOPHENOLIC ACID
Marketing authorisation
PL 20117/0065
MA holder
MORNINGSIDE HEALTHCARE LTD
MA country
XI
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Inflectra 100 mg powder for concentrate for solution for infusion

PRD6488927 · Product

Active substance
Infliximab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
00 mg milligram(s)
Max total dose
00 mg milligram(s)
Max treatment duration
9999999 Month(s)
Authorisation status
Authorised
ATC code
L04AB02 — -
Marketing authorisation
EU/1/13/854/002
MA holder
PFIZER EUROPE MA EEIG
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

274 Total trials 84 Recruiting 173 Ended
Commercial
Sponsor organisation
AstraZeneca AB
Address
-
City
Sodertalje
Postcode
151 85
Country
Sweden

Scientific contact point

Organisation
AstraZeneca AB
Contact name
Global Clinical Lead

Public contact point

Organisation
AstraZeneca AB
Contact name
AstraZeneca Clinical Study Information Center

Locations

4 EU/EEA countries · 26 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruitment ended 114 11
Germany Ongoing, recruitment ended 69 6
Italy Ongoing, recruitment ended 77 5
Spain Ongoing, recruitment ended 42 4
Rest of world
Hong Kong, Vietnam, United States, Ukraine, China, Canada, Taiwan, Japan, Brazil, India, Russian Federation, Thailand, Korea, Republic of
 — 1,302 —

Investigational sites

France

11 sites · Ongoing, recruitment ended
Centre Hospitalier Universitaire De Saint Etienne
Gastroenterology, Avenue Albert Raimond, 42270, Saint Priest En Jarez
Hopital Beaujon
Service d'Oncologie Digestive, 100 Boulevard Du General Leclerc, 92110, Clichy
C.H.U. de Montpellier - Hopital Saint Eloi
Medical oncology, 80 Av Augustin Fliche, 34295, Montpellier Cedex 5
CHU Hôtel Dieu
Hepato-gastroenterology, 1 place Alexis-Ricordeau, 44093, Nantes Cedex 1
Centre Hospitalier Universitaire De Nice
Hepato-gastroenterology, 151 Route De Saint Antoine, 06200, Nice
CHRU De Nancy
Hepato-gastroenterology, Rue Du Morvan, 54500, Vandoeuvre Les Nancy
CHU de Poitiers
Hepato-gastroenterology, 2 Rue de la Milétrie, 86021, Poitiers Cedex
Centre Hospitalier Universitaire Rouen
Medical oncology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Institut Paoli Calmettes
Medical oncology, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
Institut Gustave Roussy
Medical oncology, 114 rue Edouard-Vaillant, 94805, Villejuif Cedex
CHU Toulouse Rangueil
Digestive and Gynecological Medical Oncology, 1 avenue J. Poulhès - TSA50032, 31059, Toulouse Cedex 9

Germany

6 sites · Ongoing, recruitment ended
University Hospital Cologne AöR
Klinik für Gastroenterologie und Hepatologie, Kerpener Strasse 62, Lindenthal, Cologne
Klinikum der Universitaet Muenchen AöR
Medizinische Klinik 2 Poliklinik Gastroenterologie, Marchioninistrasse 15, Hadern, Munich
Medizinische Hochschule Hannover
Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Universitaetsklinikum Essen AöR
Gastroenterologie und Hepatologie Medizinisches Zentrum, Hufelandstrasse 55, Holsterhausen, Essen
Universitaetsklinikum Aachen AöR
Klinik für Gastroenterologie Medizinische Klinik III, Pauwelsstrasse 30, 52074, Aachen
Universitaetsklinikum Tuebingen AöR
Abteilung Innere Medizin I Hepatologie, Gastroenterologie, Infektiologie, Otfried-Mueller-Strasse 10, Nordstadt, Tuebingen

Italy

5 sites · Ongoing, recruitment ended
Azienda Ospedaliero Universitaria Pisana
U. O. ONCOLOGIA MEDICA, Via Roma 67, 56126, Pisa
Humanitas Mirasole S.p.A.
U.O.DI ONCOLOGIA MEDICA ED EMATOLOGIA, Via Alessandro Manzoni 56, 20089, Rozzano
Ospedale San Raffaele S.r.l.
U.O. Oncologia Medica, Via Olgettina 60, 20132, Milan
Azienda Ospedaliera “G. Rummo”
U.O.C. ONCOLOGIA MEDICA, Via dell’Angelo, 1, Benevento
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Dipartimento di Medicina e chirurgia traslazionale, Largo Francesco Vito 1, 00168, Rome

Spain

4 sites · Ongoing, recruitment ended
Clinica Universidad De Navarra
Unidad de Hepatología, Avenue Pio XII 36, 31008, Pamplona
Hospital Universitario Central De Asturias
Unidad de Hepatología, Avenida De Roma S/n, 33011, Oviedo
Hospital Universitario 12 De Octubre
Unidad de Hepatología, Bloque D, Avenida De Cordoba Sn, Madrid
Hospital Clinic De Barcelona
Unidad de Hepatología, Calle Villarroel 170, 08036, Barcelona

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2018-06-28 2018-07-06 2019-03-13
Germany 2018-03-14 2018-03-22 2019-06-20
Italy 2017-11-28 2017-12-06 2019-06-20
Spain 2018-02-01 2018-02-06 2019-06-20

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol lay synopsis_FR_2024-512212-21-00_Redacted 1
Protocol (for publication) D1_Protocol redacted 2024-512212-21-00 8.0
Protocol (for publication) D1_Protocol Synopsis in Lay Language_ES_2024-512212-21-00_Redacted 1.0
Protocol (for publication) D1_Protocol synopsis_FR_ 2024-512212-21_redacted 5.0
Protocol (for publication) D1_Protocol Synopsis_IT_2024-512212-21_Redacted 4
Protocol (for publication) D1_Protocol Synopsis_Lay Language Summary_country code_redacted 1
Protocol (for publication) D1_Protocol Synopsis_Lay Language Synopsis_IT_Redacted 1.0
Protocol (for publication) D1_Protocol Synopsis_Scientific Synopsis_IT_Redacted 5.0
Recruitment arrangements (for publication) CTIS Blank Document for Transition Trials n/a
Recruitment arrangements (for publication) CTIS Blank Document for Transition Trials n/a
Recruitment arrangements (for publication) CTIS Blank Document for Transition Trials n/a
Recruitment arrangements (for publication) CTIS Blank Document for Transition Trials n/a
Subject information and informed consent form (for publication) L1_ SIS and ICF Addendum-1 4
Subject information and informed consent form (for publication) L1_ SIS and ICF Addendum-2 4
Subject information and informed consent form (for publication) L1_ SIS and ICF adult subject_redacted V.13 ES
Subject information and informed consent form (for publication) L1_ SIS and ICF continuing research participants addendum-1 1
Subject information and informed consent form (for publication) L1_ SIS and ICF optional samples addendum_redacted 3
Subject information and informed consent form (for publication) L1_ SIS and ICF pregnant partners 2
Subject information and informed consent form (for publication) L1_ SIS and ICF withdrawal addendum 2
Subject information and informed consent form (for publication) L1_SIS and ICF Adult Subject German Addendum_clean 1
Subject information and informed consent form (for publication) L1_SIS and ICF Adult Subject German_redacted 11
Subject information and informed consent form (for publication) L1_SIS and ICF Adult Subject_Genetic_German_redacted 4
Subject information and informed consent form (for publication) L1_SIS and ICF_Adult participant ICF_IT_Redacted 13.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Data Privacy ICF_IT 8.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Data Privacy ICF_IT_TC 7
Subject information and informed consent form (for publication) L1_SIS and ICF_Pregnant Partner_IT 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Pregnant Partner_IT_TC 3
Subject information and informed consent form (for publication) L1_SIS and ICFs_Annex 1_FR 3
Subject information and informed consent form (for publication) L1_SIS and ICFs_Annex 2_FR 3
Subject information and informed consent form (for publication) L1_SIS and ICFs_Complementary ICF 7_FR 1
Subject information and informed consent form (for publication) L1_SIS and ICFs_Complementary ICF 8_FR 1
Subject information and informed consent form (for publication) L1_SIS and ICFs_Complementary ICF_FR 6
Subject information and informed consent form (for publication) L1_SIS and ICFs_Main_FR_Redacted 2
Subject information and informed consent form (for publication) L2_SIS and ICF_Genetic_FR_Redacted 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Sorafenib n/a

Application history

8 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-06-18 Spain Acceptable with conditions
2024-07-12
 2024-07-12
2 SUBSTANTIAL MODIFICATION SM-1 2024-12-18 Spain Acceptable
2025-02-14
 2025-02-18
3 SUBSTANTIAL MODIFICATION SM-2 2025-05-30 Spain Acceptable
2025-07-31
 2025-08-01
4 NON SUBSTANTIAL MODIFICATION NSM-1 2025-09-11 Spain Acceptable
2025-07-31
 2025-09-11
5 NON SUBSTANTIAL MODIFICATION NSM-2 2025-12-16 Spain Acceptable
2025-07-31
 2025-12-16
6 SUBSTANTIAL MODIFICATION SM-3 2026-03-06 Acceptable 2026-04-02
7 SUBSTANTIAL MODIFICATION SM-4 2026-03-09 Acceptable 2026-05-18
8 SUBSTANTIAL MODIFICATION SM-5 2026-03-17 Acceptable 2026-05-04

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