The ABC-HCC Trial: Atezolizumab Plus Bevacizumab vs. Transarterial Chemoembolization (TACE) in Intermediate-stage HepatoCellular Carcinoma

NCT04803994 | Recruiting Phase 3 DMC

• 3 other identifiers: ABC-HCC2020-004210-352024-512953-26-00
• Study Type: interventional
• Target: 434
• Locations: 6 countries
• Sites: 72

Brief Summary

The ABC-HCC trial is a Phase IIIb, randomised, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab plus bevacizumab versus TACE in patients with intermediate-stage HCC. Approximately 434 patients in two arms of treatment will be enrolled.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; HCC; intermediate stage; atezolizumab; bevacizumab; TACE

Outcome Measures

Primary Outcomes (1)

• Time to failure of treatment strategy

  The primary endpoint is defined as the time from randomization until death or need for a further therapeutic option, defined for each arm as follows: * Arm A: Time from randomization until the failure of strategy does not allow for further treatment with atezolizumab + bevacizumab; or death, whichever comes first. * Arm B: Time from randomization until the failure of strategy does not allow for further TACE therapy; or death, whichever comes first. Failure of strategy (in brief): failure of strategy is reached in case of progressive disease accompanied by any of the following: loss of clinical benefit, unacceptable toxicity, liver function deterioration, therapy not further applicable for other reasons.

  48 months - assessed every 8 weeks (±7days)

Secondary Outcomes (11)

• Overall survival (OS)

  48 months

• Overall Survival Rate at 24 months (OS@24)

  24 months

• Objective Response Rate (ORR)

  48 months

• Time to Progression (TTP)

  48 months

• Time to loss of systemic treatment options (TTSYS)

  24 months

Other Outcomes (2)

• Exploratory endpoint - Correlation of biomarkers for study endpoints

  48 months

• Exploratory endpoint - PD-L1 expression

  48 months

Study Arms (2)

Systemic therapy with atezolizumab + bevacizumab

EXPERIMENTAL

Patients receive atezolizumab 1200 mg flat dose plus bevacizumab 15 mg/kg given intravenously every 3 weeks until failure of strategy, participant request, or withdrawal of consent for a maximum of up to 24 months. The discontinuation of one of the study drugs for toxicity reasons does not qualify as failure of treatment strategy as long as the other drug can be continued according to protocol.

Drug: Atezolizumab; Drug: Bevacizumab

Locoregional therapy with TACE

ACTIVE COMPARATOR

Patients will receive initial TACE and - if required to achieve or improve an objective response - a second TACE after 8 weeks (±7 days window). Thereafter, additional TACE can be applied on demand until failure of strategy, participant request, or withdrawal of consent for a maximum of up to 24 months. TACE must be discontinued in cases of technical difficulties making additional TACE impossible. Only conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) approaches are accepted as TACE therapy. However, consistency in the TACE procedure and the use of the chemotherapeutic agent has to be maintained for each individual patient.

Procedure: TACE

Interventions

Atezolizumab DRUG

1200 mg atezolizumab intravenously Q3W (max 32 cycles, up to 24 months)

Also known as: Tecentriq

Systemic therapy with atezolizumab + bevacizumab

Bevacizumab DRUG

15 mg/kg intravenously Q3W (max 32 cycles, up to 24 months)

Also known as: Avastin

Systemic therapy with atezolizumab + bevacizumab

TACE PROCEDURE

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

Also known as: transarterial chemoembolization

Locoregional therapy with TACE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form available
• Patients\* ≥ 18 years of age at time of signing Informed Consent Form
• Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria.
• Intermediate stage HCC as defined by the following criteria:
• Disease not amenable to curative surgery, liver transplantation or curative ablation BUT disease amenable to TACE at enrollment as judged by the investigator.
• No massive multinodular pattern preventing adequate TACE
• No tumor of a diffuse infiltrative HCC type (hypovascular infiltrative tumors with ill-defined borders)
• Patent portal vein flow

You may not qualify if:

• Patients with recurrence after resection/ablation or after previous TACE are eligible, if they - according to the investigator - have an indication for (additional) TACE
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at enrollment.
• Adequate organ and bone marrow function
• Life expectancy of ≥ 3 months
• The following laboratory values obtained less than or equal to 7 days prior to randomization.
• Total bilirubin ≤ 3.0 x the upper limit of normal (ULN)
• Urine dipstick for proteinuria ≤ 2+ (within 7 days prior to randomization) Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours
• The following other laboratory values measured within 7 days prior to randomization are either normal or if abnormal do not represent a medical contraindication for TACE and atezolizumab/bevacizumab as judged by the investigator: Platelet count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine, INR or aPTT, alkaline phosphatase, neutrophil count (ANC), and serum albumin.
• Negative serum pregnancy test done lesser than or equal to 7 days prior to randomization, for females of childbearing potential only.
• No presence of untreated or incompletely treated varices with bleeding or high-risk for bleeding: Availability of esophagogastroduodenoscopy (not older than 6 months) in which all size of varices (small to large) had been assessed and varices were treated per local standard of care prior to randomization.
• Absence of other severe comorbidities
• Resolution of any acute, clinically significant treatment-related adverse events from prior therapy/procedure to Grade ≤ 1 prior to randomization, with the exception of alopecia.
• For patients with active hepatitis B virus (HBV):
• HBV DNA ≤ 2000 IU/mL obtained within 28 days prior to randomization, AND
• Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (72)

LKH - Univ. Klinikum Graz

Graz, 8036, Austria

RECRUITING

Medzinische Universität Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Klinikum Klagenfurt am Wörthersee

Klagenfurt, 9020, Austria

RECRUITING

Ordensklinikum Linz

Linz, 4010, Austria

RECRUITING

Universitätsklinikum St. Pölten

Sankt Pölten, 3100, Austria

RECRUITING

Medizinische Universität Wien

Vienna, 1090, Austria

RECRUITING

Institut Sainte-Catherine

Avignon, 84918, France

RECRUITING

Hôpital Jean-Verdier Avicenne

Bobigny, 93000, France

RECRUITING

CHU Bordeaux

Bordeaux, 33000, France

RECRUITING

CHU Clermont-Ferrand CHU Estaing

Clermont-Ferrand, 63100, France

RECRUITING

Beaujon Hospital

Clichy, 92110, France

RECRUITING

CHU Grenoble

Grenoble, 38700, France

RECRUITING

Croix-Rousse Hopital

Lyon, 69004, France

RECRUITING

Saint Joseph Hopital - Marseille

Marseille, 13008, France

RECRUITING

Hôpital Universitaire Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Centre Hépato-biliaire Paul Brousse

Villejuif, 94800, France

RECRUITING

University Hospital RWTH Aachen

Aachen, 52074, Germany

RECRUITING

Klinikum St. Marien Amberg

Amberg, 92224, Germany

RECRUITING

Vivantes Klinikum Neukölln

Berlin, 12351, Germany

RECRUITING

Universitätsklinikum Bochum

Bochum, 44892, Germany

RECRUITING

Uniklinik Köln

Cologne, 50937, Germany

RECRUITING

Universitätsklinikum Dresden

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

RECRUITING

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Klinikum Konstanz

Konstanz, 78464, Germany

RECRUITING

Krankenhaus Maria-Hilf Krefeld

Krefeld, 47805, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

RECRUITING

Universitätsmedizin Mainz

Mainz, 55131, Germany

RECRUITING

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

RECRUITING

Universitätsklinikum Marburg

Marburg, 35043, Germany

RECRUITING

Klinikum rechts der Isar München

München, 81675, Germany

RECRUITING

Klinikum Mutterhaus Trier

Trier, 54290, Germany

RECRUITING

Krankenhaus der Barmherzigen Brüder Trier

Trier, 54292, Germany

RECRUITING

Uniklinik Ulm

Ulm, 89070, Germany

RECRUITING

St. Josefs Hospital Wiesbaden

Wiesbaden, 65189, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, 97078, Germany

RECRUITING

Policlinico S. Orsola Bologna

Bologna, 40138, Italy

RECRUITING

Instituto Tumori della Romagna IRST IRCCS

Meldola, 47014, Italy

RECRUITING

Policlinico di Milano

Milan, 20122, Italy

RECRUITING

Instituto di Tumori

Milan, 20133, Italy

RECRUITING

Università di Pisa (UNIPI)

Pisa, 56124, Italy

RECRUITING

AOUI Verona

Verona, 37126, Italy

RECRUITING

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

RECRUITING

Kobe University Hospital

Kobe, 650-0017, Japan

RECRUITING

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

RECRUITING

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

RECRUITING

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

RECRUITING

Kindai University Hospital

Osaka, 589-8511, Japan

RECRUITING

Saitama Medical University Hospital

Saitama, 350-0451, Japan

RECRUITING

Fujita Health University Hospital

Toyoake, 470-1192, Japan

RECRUITING

Yamaguchi University Hospital

Ube, 755-0046, Japan

RECRUITING

Hospital Universitario de Alicante

Alicante, 03010, Spain

RECRUITING

Hospital Infanta Cristina

Badajoz, 06080, Spain

RECRUITING

Hospital Germans Trias I Pujol

Badalona, 08916, Spain

RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Barcelona Clinic Liver Cancer, Universitat de Bracelona

Barcelona, 08036, Spain

RECRUITING

Hospital Puerta del Mar

Cadiz, 11009, Spain

RECRUITING

Hospital de Jaen

Jaén, 23007, Spain

RECRUITING

Hospital Universitario Gregorio Marañon

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Fundación Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222, Spain

RECRUITING

Hospital de Alcorcón

Madrid, 28922, Spain

RECRUITING

Hospital de Málaga

Málaga, 29010, Spain

RECRUITING

Hospital Marqués de Valdecilla

Santander, 39008, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Germany

  STUDY DIRECTOR

• Peter Galle, Prof. Dr.

  Universitätsmedizin Mainz, Germany

  PRINCIPAL INVESTIGATOR

• Jordi Bruix, Prof. Dr.

  Barcelona Clinic Liver Cancer, Universitat de Barcelona, Spain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Galle, Prof. Dr.

CONTACT

0049 6131 177275; peter.galle@unimedizin-mainz.de

Johanna Riedel, Dr.

CONTACT

0049 697 601 4635; riedel.johanna@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Clinical trial with two study arms: Experimental arm A: 50% of the patients will receive a combination therapy (systemic) of the monoclonal antibodies atezolizumab and bevacizumab. Control arm B: 50% of the patients will receive TACE therapy (locoregional).

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 18, 2021
• Study Start: July 6, 2021
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (9); DE (26); ES (15); AU (6); FR (10); IT (6)