Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
897
Countries
5
Sites
33
Histologically or cytologically confirmed Locoregional Hepatocellular Carcinoma (HCC) and successfully completed curative therapy (resection or ablation)
To assess the efficacy of durvalumab in combination with bevacizumab compared to placebo in terms of Recurrence-free survival (RFS)
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
- 7 Oct 2019 → ongoing
- Decision date (initial)
- 2024-03-19
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- AstraZeneca AB
External identifiers
- EU CT number
- 2023-507689-26-00
- EudraCT number
- 2018-004105-85
- ClinicalTrials.gov
- NCT03847428
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacokinetic, Safety, Therapy, Pharmacoeconomic, Pharmacogenetic
To assess the efficacy of durvalumab in combination with bevacizumab compared to placebo in terms of Recurrence-free survival (RFS)
Secondary objectives 1
- To compare the efficacy of Arm B versus Arm C in terms of RFS To assess the efficacy of Arm A vs Arm C and Arm B vs Arm C in terms of other efficacy endpoints (i.e. RFS24, RFS36, TTR, OS, RFS/PFS2)
Conditions and MedDRA coding
Histologically or cytologically confirmed Locoregional Hepatocellular Carcinoma (HCC) and successfully completed curative therapy (resection or ablation)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10077746 | Hepatocellular carcinoma stage I | 10029104 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening Participants will undergo screening evaluations to determine eligibility within 28 days prior to randomization.
|
Randomised Controlled | Double | [{"id":151242,"code":3,"name":"Monitor"},{"id":151241,"code":1,"name":"Subject"},{"id":151243,"code":2,"name":"Investigator"}] | Arm A: Arm A: Durvalumab + bevacizumab Q3W for 12 months Arm B: Arm B: Durvalumab + bevacizumab placebo Q3W for 12 months Arm C: Arm C: Durvalumab placebo + bevacizumab placebo Q3W for 12 months |
| 2 | Treatment All participants will be randomized in a 1:1:1 ratio to one of the following treatment groups: Arm A, Arm B or Arm C
|
Randomised Controlled | Double | [{"id":151246,"code":3,"name":"Monitor"},{"id":151245,"code":1,"name":"Subject"},{"id":151247,"code":2,"name":"Investigator"}] | Arm A: Arm A: Durvalumab + bevacizumab Q3W for 12 months Arm B: Arm B: Durvalumab + bevacizumab placebo Q3W for 12 months Arm C: Arm C: Durvalumab placebo + bevacizumab placebo Q3W for 12 months |
| 3 | Subjects that completed/discontinued treatment Patients that completed/discontinued study treatment will still continue in the study for recurrence, safety and survival follow up until the end of the study.
|
Randomised Controlled | Double | [{"id":151250,"code":2,"name":"Investigator"},{"id":151249,"code":3,"name":"Monitor"},{"id":151251,"code":1,"name":"Subject"}] | Arm A: Arm A: Durvalumab + bevacizumab Q3W for 12 months Arm B: Arm B: Durvalumab + bevacizumab placebo Q3W for 12 months Arm C: Arm C: Durvalumab placebo + bevacizumab placebo Q3W for 12 months |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- Yes
- IPD plan description
- Qualified researchers can request access to anonymized individual patient-level data from. AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- 1.Histologically or cytologically (or radiologically for patients undergoing curative ablation), newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation) 2.Imaging to confirm disease-free status within 28 days prior to randomization 3.ECOG 0-1 at enrolment 4.Child-Pugh score of 5 or 6 5.Patients with HBV infection must receive antiviral therapy at least after enrollment per institutional practice to ensure adequate viral suppression prior to randomization. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. 6.Patients with HCV infection must be managed per local institutional practice for the study. 7.Adequate organ and marrow function, as defined by the CSP
Exclusion criteria 1
- 1.Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC 2.Evidence of metastasis, macrovascular invasion or co-existing malignant disease on baseline imaging. 3.History of hepatic encephalopathy within 12 months prior to randomization 4.Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging 5.Patients with Vp1 to Vp4 portal vein thrombosis on baseline imaging are excluded. 6.Active co-infection with HBV and HDV. 7.Receipt of prior systemic anticancer therapy for HCC 8.Those on a waiting list for liver transplantation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Recurrence-free survival (RFS)
Secondary endpoints 1
- Overall survival (OS) Time to recurrence (TTR) RFS at 24 months (RFS24) and RFS at 36 months (RFS36) Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
IMFINZI 50 mg/mL concentrate for solution for infusion.
PRD6651663 · Product
- Active substance
- Durvalumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC28 — -
- Marketing authorisation
- EU/1/18/1322/002
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB16402MIG · Substance
- Active substance
- Bevacizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 2
SUB29101 · Substance
- Active substance
- Dextrose Bp
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12581MIG · Substance
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 2
SUB02681MIG · Substance
- Active substance
- Infliximab
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB03360MIG · Substance
- 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
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Astrazeneca AB
- Sponsor organisation
- Astrazeneca AB
- Address
- Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674
- City
- Sodertalje
- Postcode
- 151 85
- Country
- Sweden
Scientific contact point
- Organisation
- Astrazeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Public contact point
- Organisation
- Astrazeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Locations
5 EU/EEA countries · 33 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruiting | 4 | 2 |
| France | Ongoing, recruiting | 43 | 11 |
| Germany | Ongoing, recruiting | 18 | 8 |
| Italy | Ongoing, recruiting | 24 | 8 |
| Poland | Ongoing, recruiting | 5 | 4 |
| Rest of world
Brazil, Japan, Peru, Vietnam, Australia, Thailand, Hong Kong, Canada, India, Taiwan, Korea, Republic of, Egypt, China, United States, Turkey, Russian Federation, Philippines, Singapore
|
— | 803 | — |
Investigational sites
Ordensklinikum Linz GmbH
Internal I: Medical Oncology and Hematology Study coordination, Seilerstaette 4, 4010, Linz
Noe LGA Gesundheit Region Mitte GmbH
2. Medical Department, Dunant-Platz 1, 3100, St. Poelten
Centre Hospitalier Regional Universitaire De Tours
Hépato-gastroentérologie et Cancérologie Digestive, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Hopital Saint Antoine
Service d'hépato-gastro-entérologie, 184 Rue Du Faubourg Saint Antoine, 75571, Paris Cedex 12
Centre Hospitalier Universitaire De Dijon
Service d'Hépato-gastro et oncologie digestive, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Universitaire De Bordeaux
Service d'Hépato-gastro-entérologie et oncologie digestive, Avenue De Magellan, 33600, Pessac
Centre Hospitalier Universitaire De Toulouse
Hépatologie, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9
Centre Hospitalier Universitaire De Nice
Pôle de Référence Hépato Gastro-entérologie et Oncologie Digestive, 151 Route De Saint Antoine, 06200, Nice
Hopital Beaujon
Service d'Oncologie Digestive, 100 Boulevard Du General Leclerc, 92110, Clichy
Besancon University Hospital Center
Service Hepatologie, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier Universitaire D'Angers
Service d'Hepato-Gastroentérologie, 4 Rue Larrey, 49100, Angers
Centre Hospitalier Universitaire Amiens Picardie
Service d’Hépato-Gastroentérologie, 1 Rond Point Du Pr Christian Cabrol, 80054, Amiens Cedex 1
Centre Hospitalier Universitaire De Nantes
Service d'hépatogastro-entérologie, 1 Place Alexis Ricordeau, 44000, Nantes
Universitaetsklinikum Bonn AöR
"Medizinische Klinik und Poliklinik I Onkologische Gastroenterologie", Venusberg-Campus 1, Venusberg, Bonn
Medical Center - University Of Freiburg
Department Chirurgie Klinik für Allgemein- und Viszeralchirurgie, Hugstetter Strasse 55, Stuehlinger, Freiburg Im Breisgau
Universitaetsklinikum Tuebingen AöR
Innere Medizin I Hepatologie, Gastroenterologie, Infektologie, Otfried-Mueller-Strasse 10, Nordstadt, Tuebingen
University Hospital Cologne AöR
Klinik für Gastroenterologie und Hepatologie, Kerpener Strasse 62, Lindenthal, Cologne
Universitaetsklinikum Schleswig-Holstein
Medizinische Klinik I Studienzentrale MKI, Haus D6, Ratzeburger Allee 160, Luebeck
Klinikum der Universitaet Muenchen AöR
Medizinische Klinik und Poliklinik II, Marchioninistrasse 15, Hadern, Munich
Klinikum Chemnitz gGmbH
Klinik für Gastroenterologie /Gastroenterologische Onkologie, Flemmingstrasse 2, Altendorf, Chemnitz
Charite Universitaetsmedizin Berlin KöR
Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Augustenburger Platz 1, Wedding, Berlin
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Basso, Largo Francesco Vito 1, 00168, Rome
Ospedale San Raffaele S.r.l.
Oncology, Via Olgettina 60, 20132, Milan
Pia Fondazione Di Culto E Religione Card G Panico
Oncology, Via Pio X 4, 73039, Tricase
ASST Grande Ospedale Metropolitano Niguarda
Oncologia Falck, Piazza Dell'ospedale Maggiore 3, 20162, Milan
IRCCS Istituto Nazionale Tumori Fondazione Pascale
abdominal Oncology, Via Mariano Semmola 52, 80131, Naples
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Oncology, Piazza Luigi Miraglia 2, 80138, Naples
Universita Degli Studi Di Verona
Oncology, Piazzale La Scuro, 37134, Verona
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department of Digestive System, Via Pietro Albertoni 15, 40138, Bologna
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Onkologii i Radioterapii, Ul. Wawelska 15, 02-034, Warsaw
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Ambulatorium Chemioterapii i Oddział Kliniczny Radioterapii, Ul. Izabeli Romanowskiej 2, 85-796, Bydgoszcz
Uniwersyteckie Centrum Kliniczne
Klinika Onkologii i Radioterapii, Ul. Mariana Smoluchowskiego 17, 80-214, Gdansk
Wielkopolskie Centrum Onkologii Im. Marii Sklodowskiej-Curie
N/A, Ul. Garbary 15, 61-866, Poznan
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2019-10-07 | 2020-02-14 | |||
| France | 2019-10-24 | 2020-01-16 | |||
| Germany | 2019-12-02 | 2020-05-04 | |||
| Italy | 2019-11-27 | 2020-04-23 | |||
| Poland | 2021-05-17 | 2021-05-17 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-28583
- Sponsor became aware
- 2024-05-31
- Date of breach
- 2024-06-05
- Submission date
- 2024-06-07
- Member states concerned
- Austria, France, Germany, Italy, Poland
- Categories
- Regulation
- Areas impacted
- Data reliability or robustness, Regulatory
- Benefit-risk balance changed
- No
- Description
- Isolated fraudulent activity detected in affected third country (Japan) with an individual outsourced clinical research associate involved with the study.
- Sponsor actions
- Access to the study has been revoked from clinical research associate. Investigation is ongoing including on-site investigations to define extent of fraudulent activities and site data verification to ensure study integrity. No evidence of impropriety by the impacted clinical trial sites. To date, no risks to patient safety identified.
| Organisation | City | Country | Type |
|---|---|---|---|
| EPS Corp. | Shinjuku-Ku | Japan | CRO |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_EN 2023-507689-26-00 redacted | 4 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_placeholder | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_placeholder | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and Adult Subject Addendum redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult participant Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult Subject Part II German redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Future Research Part II German | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partners clean | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G1_SmPC-Bevacizumab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Non-AZ IMP Reference Safety Information_Bevacizumab | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_AT_2023-507689-26-00_redacted | 4 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_IT_2023-507689-26-00_redacted | 5 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Lay Language_FR_2023-507689-26_For Publication | 0.12 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Lay Language_IT_2023-507689-26_For publication | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Lay Language_PL_2023-507689-26_For publication | 1 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-01-15 | Austria | Acceptable 2024-03-19
|
2024-03-19 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-05-09 | Austria | Acceptable 2024-07-15
|
2024-07-17 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-09-26 | Austria | Acceptable 2024-12-02
|
2024-12-03 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-28 | Acceptable | 2025-05-09 | |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-10-14 | Austria | Acceptable | 2025-10-14 |