Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
674
Countries
3
Sites
17
Locoregional Hepatocellular Carcinoma (HCC)
To assess the efficacy of durvalumab and bevacizumab when given with transarterial chemoembolization (TACE) compared to TACE + placebo
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
- 17 Jul 2019 → 23 Mar 2026
- Decision date (initial)
- 2024-02-21
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- AstraZeneca AB
External identifiers
- EU CT number
- 2023-509053-32-00
- EudraCT number
- 2018-002134-20
- ClinicalTrials.gov
- NCT03778957
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
To assess the efficacy of durvalumab and bevacizumab when given with transarterial chemoembolization (TACE) compared to TACE + placebo
Secondary objectives 1
- To assess the efficacy and safety of durvalumab when given with TACE compared To TACE and placebo. To assess the efficacy of all immunotherapy arms and TACE compared with TACE and placebo by PD-L1 expression and AFP expression level. To assess disease-related symptoms and health-related quality of life (HRQoL) in patients treated with all immunotherapy arms and TACE compared with TACE and placebo. To evaluate the PK and immunogenicities of all immunotherapy arms with TACE.
Conditions and MedDRA coding
Locoregional Hepatocellular Carcinoma (HCC)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10019828 | Hepatocellular carcinoma non-resectable | 10029104 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | NA NA
|
Randomised Controlled | Double | [{"id":141645,"code":1,"name":"Subject"},{"id":141643,"code":3,"name":"Monitor"},{"id":141644,"code":2,"name":"Investigator"}] | Arm A: Transarterial Chemoembolization (TACE) in combination with Durvalumab |
| 2 | NA NA
|
Randomised Controlled | Double | [{"id":141649,"code":3,"name":"Monitor"},{"id":141647,"code":1,"name":"Subject"},{"id":141648,"code":2,"name":"Investigator"}] | Arm B: Transarterial Chemoembolization (TACE) in combination with Durvalumab and Bevacizumab |
| 3 | NA NA
|
Randomised Controlled | Double | [{"id":141652,"code":3,"name":"Monitor"},{"id":141653,"code":1,"name":"Subject"},{"id":141651,"code":2,"name":"Investigator"}] | Arm C: Transarterial Chemoembolization (TACE) in combination with Placebos |
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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- No evidence of extrahepatic disease. Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE. Child-Pugh score class A to B7 and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment. Measurable disease by mRECIST criteria. Adequate organ and marrow function.
Exclusion criteria 1
- Any history of nephrotic or nephritic syndrome. Clinically significant cardiovascular disease or arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization. Any prior or current evidence of coagulopathy or bleeding diathesis or patients who had any kind of surgery in the past 28 days (biopsies are exempt from this exclusion). History of abdominal fistula or GI perforation, non healed gastric ulcer, or active GI bleeding within 6 months prior to enrollment. Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR
Secondary endpoints 1
- Overall Survival (OS). Objective Response Rate (ORR). Disease Control Rate (DCR). Duration of Response (DoR). Time to progression (TTP). Time from Randomization to Second Progression PFS (PFS2). Health-related quality of life (HRQoL) patient reported outcomes.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
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 USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 99 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
SUB16402MIG · Substance
- Active substance
- Bevacizumab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 99 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP29096188 · ATC
- Active substance
- Bevacizumab
- Substance synonyms
- BI 695502, BS-503A, PF-06439535, BP01, HLX04, RHUMAB-VEGF, BEVACIZUMABUM, RHUMAB VEGF
- Route of administration
- INTRAVENOUS
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 99 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC07 — BEVACIZUMAB
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 2
SUB03360MIG · Substance
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- CAPSULES
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 99 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02681MIG · Substance
- Active substance
- Infliximab
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 99 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
- -
- 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
3 EU/EEA countries · 17 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 53 | 9 |
| Italy | Ended | 13 | 4 |
| Spain | Ended | 10 | 4 |
| Rest of world
Japan, Australia, Brazil, Taiwan, India, Hong Kong, Thailand, Singapore, Korea, Republic of, United States, China, Canada, Vietnam, Russian Federation, Mexico
|
— | 598 | — |
Investigational sites
Centre Hospitalier Universitaire De Nice
Hepatogastro-enterology & Digestive Oncology, 151 Route De Saint Antoine, 06200, Nice
Hopital Beaujon
Medical Oncology, 100 Boulevard Du General Leclerc, 92110, Clichy
Hopital Saint Eloi
Medical Oncology, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Assistance Publique Hopitaux De Paris
Hepatology, 43 Boulevard De L Hopital, 75013, Paris
Centre Hospitalier Universitaire De Bordeaux
Digestive Oncology, Avenue De Magellan, 33600, Pessac
Hopital Avicenne
Hepatogastro-enterology, 125 Rue De Stalingrad, 93009, Bobigny Cedex
CHRU De Nancy
Hepatogastro-enterology, Vandoeuvre-Les-Nancy Cedex, 11 Rue Du Morvan, Vandoeuvre Les Nancy Cedex
Centre Hospitalier Universitaire Grenoble Alpes
Hepatogastro-enterology, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Universitaire De Toulouse
Medical Oncology, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Oncology, Piazzale Spedali Civili 1, 25123, Brescia
Azienda USL Toscana Sud Est
Oncology, Ospedale Area Aretina Nord, Via Pietro Nenni 20/22, Arezzo
Fondazione IRCCS Istituto Nazionale Dei Tumori
Oncology General Surgery, Via Giacomo Venezian 1, 20133, Milan
Azienda Ospedaliero Universitaria Pisana
Oncology, Via Roma 67, 56126, Pisa
Clinica Universidad De Navarra
Unidad de Hepatología, Avenue Pio XII 36, 31008, Pamplona
Hospital General Universitario Gregorio Maranon
Unidad de Hepatología, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Donostia
Servicio Digestivo, Pasealeku Doct. Begiristain 109, 20014, Donostia
Hospital General Universitario Reina Sofia
Servicio de Hepatología-Transplante hepático, Avenida Menendez Pidal S/n, 14004, Cordoba
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 |
|---|---|---|---|---|---|
| France | 2019-07-30 | 2026-04-07 | 2019-08-26 | 2021-07-19 | |
| Italy | 2019-07-25 | 2026-03-25 | 2019-11-06 | 2021-06-29 | |
| Spain | 2019-07-17 | 2026-03-23 | 2019-12-20 | 2021-02-17 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-509053-32-00_Redacted | 2 |
| Recruitment arrangements (for publication) | CTIS Blank Document for Transition Trials | NA |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult subject annex_redacted | 5.0 ES |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult subject_redacted | 12 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partners_clean | 3.0 ES |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Bevacizumab 25 mg-ml concentrate for solution for infusion | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Durvalumab_placeholder | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_Non-AZ IMP Reference Safety Information_nRSI Bevacizumab | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ES_2023-509053-32-00_redacted | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_IT_2023-509053-32-00_redacted | 5 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Lay Language_ES_2023-509053-32-00_for publication | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_Lay Language_FR_2023-509053-32-00_for publication | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_Lay Language_IT_2023-509053-32-00_for publication | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-01-17 | Spain | Acceptable 2024-02-16
|
2024-02-16 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-03-21 | Spain | Acceptable 2024-06-13
|
2024-06-13 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-10-09 | Spain | Acceptable 2024-11-12
|
2024-11-12 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-10-14 | Spain | Acceptable 2024-11-12
|
2025-10-14 |