Clinical trial • Phase III • Oncology

NIVOLUMAB for Hepatocellular carcinoma

Phase III trial of NIVOLUMAB for Hepatocellular carcinoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Hepatocellular carcinoma
Trial Stage
Phase III
Drug Modality
Monoclonal antibody

Key dates

Initial CTIS Submission Date
23-01-2024
First CTIS Authorization Date
22-02-2024

Trial design

Randomised, placebo (5% dextrose injection or 0.9% sodium chloride injection) - comparator described as placebo solution; specific dose and administration schedule for placebo not specified in the available data.-controlled Phase III trial in Romania, Austria, Germany and others.

Randomised
Yes
Comparator
Placebo (5% Dextrose injection or 0.9% Sodium Chloride injection) - comparator described as placebo solution; specific dose and administration schedule for placebo not specified in the available data.
Target Sample Size
651

Eligibility

Recruits 651 Vulnerable population is selected (isVulnerablePopulationSelected: true). Multiple country-specific subject information and informed consent forms (ICFs) are listed in the dossier, but explicit details on assent/consent handling for vulnerable participants are not provided in the available data..

Pregnancy Exclusion
Positive pregnancy test.
Vulnerable Population
Vulnerable population is selected (isVulnerablePopulationSelected: true). Multiple country-specific subject information and informed consent forms (ICFs) are listed in the dossier, but explicit details on assent/consent handling for vulnerable participants are not provided in the available data.

Inclusion criteria

  • {"criterion_text":"- Males and females, ages 18 or older.\n- Participants must have a first diagnosis of HCC amenable for management with curative intent by resection or local ablation.\n- Participants are eligible to enroll if they have non-viral related-HCC, or if they have HBV-HCC, or HCV-HCC.\n- Participants are eligible to enroll if they have undergone: i) Hepatic resection and have the following tumor characteristics: up to three tumors, at least one with a diameter > 5 cm OR none with a diameter > 5 cm but with confirmation of microvascular invasion or poorly /undifferentiated HCC; or more than three tumors, none with a diameter > 5 cm ii) Local ablation [radiofrequency ablation (RFA) or microwave ablation (MWA)] and have the following tumor characteristics: solitary tumor > 3cm but <=5 cm; OR Multiple tumors (up to 4), none with a diameter > 5 cm\n- Participants must have complete resection response, or must have achieved radiologically documented complete resection after local ablation.\n- All participants are required to have imaging studies confirming disease-free status at least 4 weeks after either complete tumor removal after surgical resection or local ablation, and within 4 weeks prior to randomization.\n- Child-Pugh Score 5 or 6.\n- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1."}

Exclusion criteria

  • {"criterion_text":"- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.\n- Prior recurrence of HCC.\n- Any evidence of tumor metastasis or co-existing malignant disease.\n- Participants showing evidence of macrovascular invasion on imaging tests.\n- Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation.\n- Active co-infection with both Hepatitis B and C, OR Hepatitis D and B.\n- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).\n- Participants with an active, known or suspected autoimmune disease.\n- Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment.\n- Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.\n- Participants previously receiving any prior therapy for HCC, including loco-regional therapies, before or after resection or ablation.\n- Participants receiving or expected to receive IFN-based therapies during the study period.\n- Positive pregnancy test."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Recurrence free survival (RFS), defined as the time from randomization to the first documented disease recurrence or death (by any cause), whichever occurs first.","definition_or_measurement_approach":"Defined as the time from randomization to the first documented disease recurrence or death (by any cause), whichever occurs first. (BICR assessment referenced in objectives.)"}

Secondary endpoints

  • {"endpoint_text":"- OS, defined as the time between the date of randomization and the date of death (by any cause).","definition_or_measurement_approach":"Defined as the time between the date of randomization and the date of death (by any cause)."}
  • {"endpoint_text":"- Time to Recurrence (TTR), defined as the time from randomization to the first documented disease recurrence.","definition_or_measurement_approach":"Defined as the time from randomization to the first documented disease recurrence. (BICR assessment referenced for TTR in objectives.)"}

Recruitment

Planned Sample Size
651
Recruitment Window Months
153
Consent Approach
Informed consent is required; multiple country-specific Subject Information Sheets and Informed Consent Forms (ICFs) are listed in the documents (L1 SIS and ICF main and addenda for multiple Member States). The available metadata does not provide the full text of consent/assent procedures or languages beyond the presence of country-specific ICF documents.

Geography

Total Number Of Sites
42
Total Number Of Participants
145

Romania

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
799
Number Of Sites
3
Number Of Participants
11

Sites

Site Name
Centrul De Oncologie SF Nectarie S.R.L.
Department Name
Oncologie Medicala
Contact Person Name
Michael Schenker
Contact Person Email
mike_schenker@yahoo.com
Site Name
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
Department Name
Oncologie
Contact Person Name
Tudor Ciuleanu
Contact Person Email
tudor_ciuleanu@hotmail.com
Site Name
Institutul Clinic Fundeni
Department Name
Oncologie Medicala
Contact Person Name
Adina Croitoru
Contact Person Email
adina.croitoru09@yahoo.com

Austria

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
794
Number Of Sites
3
Number Of Participants
7

Sites

Site Name
Medical University of Graz
Department Name
Department of Gastroenterology and Hepatology Hepatology
Contact Person Name
Rudolf Stauber
Contact Person Email
rudolf.stauber@medunigraz.at
Site Name
Klinik Favoriten
Department Name
Department of Surgery Heopato-Pancreato-Billary Center
Contact Person Name
Thomas Gruenberger
Contact Person Email
tgruenberger@icloud.com
Site Name
Medical University Of Vienna
Department Name
Department of Gastroenterology & Hepatology
Contact Person Name
Matthias Pinter

Germany

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
795
Number Of Sites
4
Number Of Participants
10

Sites

Site Name
Universitaetsklinikum Essen AöR
Department Name
Gastroenterologie und Hepatologie, 1. OG, Raum 1.160
Contact Person Name
Hartmut Schmidt
Contact Person Email
hartmut.schmidt@uk-essen.de
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Medizinische Klinik und Poliklinik I Privatambulanz
Contact Person Name
Christian P. Strassburg
Contact Person Email
christian.strassburg@ukbonn.de
Site Name
Goethe University Frankfurt
Department Name
Medizinische Klinik 1
Contact Person Name
Joerg Trojan
Contact Person Email
trojan@em.uni-frankfurt.de
Site Name
Otto Von Guericke Universitaet Magdeburg
Department Name
Klinik für Gastroenterologie, Hepatologie und Infektologie
Contact Person Name
Marino Venerito
Contact Person Email
m.venerito@med.ovgu.de

Spain

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
795
Number Of Sites
8
Number Of Participants
17

Sites

Site Name
Hospital Clinic De Barcelona
Department Name
HEPATIC ONCOLOGY
Contact Person Name
Maria Reig
Contact Person Email
mreig1@clinic.cat
Site Name
Hospital Universitari Vall D Hebron
Department Name
Liver Unit - Department of Internal Medicine
Contact Person Name
Beatriz Minguez Rosique
Contact Person Email
beatriz.minguez@vallhebron.cat
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Gastroenterology
Contact Person Name
Ana Matilla Pena
Contact Person Email
xxxxxxx@xxx.com
Site Name
Hospital Unviersitario Miguel Servet
Department Name
Oncology
Contact Person Name
Roberto Pazo Cid
Contact Person Email
rpazo@salud.aragon.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hepatology
Contact Person Name
Maria Teresa Ferrer
Contact Person Email
xxxxx@xxx.com
Site Name
Hospital Universitario Donostia
Department Name
Digestive
Contact Person Name
IDOIA UGARTEBURU SORALUCE
Site Name
Parc Tauli Hospital Universitari
Department Name
Gastroenterology-Hepatology
Contact Person Name
Mercedes Vergara Gómez
Contact Person Email
mvergara@tauli.cat
Site Name
Hospital General Universitario Reina Sofia
Department Name
Gastroenterology
Contact Person Name
Jose Montero Alvarez
Contact Person Email
xxxx@xxx.com

France

Earliest CTIS Part Ii Submission Date
20-02-2024
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
779
Number Of Sites
12
Number Of Participants
62

Sites

Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Hepato-Gastroenterology
Contact Person Name
Thomas Decaens
Contact Person Email
tdecaens@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Hepato-Gastroenterology
Contact Person Name
Edouard BARDOU-JACQUET
Site Name
Hopital Paul Brousse
Department Name
Hepatobiliary
Contact Person Name
Olivier Rosmorduc
Contact Person Email
olivier.rosmorduc@aphp.fr
Site Name
Hopital Beaujon
Department Name
Digestive Oncology
Contact Person Name
Mohamed Bouattour
Contact Person Email
mohamed.bouattour@aphp.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Medical Oncology
Contact Person Name
Eric Assenat
Contact Person Email
e-assenat@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire Reims
Department Name
Hepato-Gastroenterology and Digestive Oncology
Contact Person Name
Alexandra Heurgue-Berlot
Contact Person Email
aheurgue@chu-reims.fr
Site Name
CHRU De Nancy
Department Name
Hepato-Gastroenterology
Contact Person Name
Jean-Pierre Bronowicki
Contact Person Email
jp.bronowicki@chru-nancy.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Digestive System Diseases and Nutrition
Contact Person Name
Sébastien Dharancy
Site Name
Assistance Publique Hopitaux De Paris (Creteil)
Department Name
Hepatology
Contact Person Name
Hélène Regnault
Contact Person Email
helene.regnault@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris (Bobigny)
Department Name
Hepato-Gastroenterology
Contact Person Name
Véronique Grando-Lemaire
Contact Person Email
Veronique.grando@aphp.fr
Site Name
Hopital De La Croix Rousse
Department Name
Hepatology
Contact Person Name
Philippe Merle
Contact Person Email
philippe.merle@inserm.fr
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
Oncology and Hematology
Contact Person Name
Jean-Philippe Metges

Italy

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
792
Number Of Sites
8
Number Of Participants
30

Sites

Site Name
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Department Name
Medicina Clinica e Sperimentale
Contact Person Name
Carlo Saitta
Contact Person Email
carlo.saitta@unime.it
Site Name
Azienda Ospedaliero-Universitaria Di Cagliari
Department Name
Oncologia Medica
Contact Person Name
Mario Scartozzi
Contact Person Email
marioscartozzi@unica.it
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia
Contact Person Name
Sara Lonardi
Contact Person Email
sara.lonardi@iov.veneto.it
Site Name
Careggi University Hospital
Department Name
Oncologia Medica
Contact Person Name
Lorenzo Antonuzzo
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Medicina Interna e Gastroenterologia
Contact Person Name
Antonio Gasbarrini
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Medicina Interna
Contact Person Name
Fabio Piscaglia
Contact Person Email
fabio.piscaglia@unibo.it
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Chirurgia oncologica
Contact Person Name
Vincenzo Mazzaferro
Site Name
Azienda Ospedaliera Dei Colli
Department Name
Oncologia
Contact Person Name
Vincenzo Montesarchio

Netherlands

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
792
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
University Hospital Maastricht
Department Name
Oncology
Contact Person Name
Judith De Vos
Contact Person Email
judith.de.vos@mumc.nl

Belgium

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
792
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
UZ Leuven
Department Name
Internal medicine - hepatology
Contact Person Name
Chris Verslype
Contact Person Email
chris.verslype@uzleuven.be
Site Name
Hopital Erasme
Department Name
Gastroenterology
Contact Person Name
Gontran Verset
Contact Person Email
gontran.verset@hubruxelles.be
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Hepatogastroenerology
Contact Person Name
Ivan Borbath

Sponsor

Primary sponsor

Full Name
Bristol-Myers Squibb Services Unlimited Company
Organisation Type
Pharmaceutical company
Country Of Registered Address
Ireland

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Prj Mgmt; Ctry/Site Sel & Mgmt; Invst Pymts; Drug Accntblty;3rd pty vendor mgmt; Stdy File Mgmt, IVRS – treatment randomisation

Third parties

  • {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"Specialty Biomarker Laboratory, IHC Biomarker expression analysis (PD-L1), CD8, MHCI, PD-1 H&E, stain, scribe and pathology review for downstream genomics analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Data entry of Local Laboratory Values","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"PD-L1 CPS scoring of slides stained at Mosaic,Histopathology","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Prj Mgmt; Ctry/Site Sel & Mgmt; Invst Pymts; Drug Accntblty;3rd pty vendor mgmt; Stdy File Mgmt, IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q2 Solutions","duties_or_roles":"Myeloid derived suppressor Cell analysis (MDSC)","organisation_type":"SME"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Sample storage for serum samples, ctDNA plasma samples, PB DNA samples, RNAlater samples, tissue samples, pathology reports","organisation_type":"Pharmaceutical company"}
  • {"country":"India","full_name":"Accenture Solutions Private Limited","duties_or_roles":"Embarc operations","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Provides electronic payments, travel arrangements,electronic study-related comunications to patients","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"India","full_name":"Syngene International Limited","duties_or_roles":"PK/Immunogenicity Nivolumab (ex-China)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Lag III assay","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
OPDIVO 10 mg/mL concentrate for solution for infusion.
Active Substance
NIVOLUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation EU/1/15/1014/002)
Maximum Dose
Max daily dose amount 480 mg (as listed in product metadata)
Investigational Product Name
5% Dextrose injection; Solution for injection/infusion (placebo)
Modality
Other
Investigational Product Name
0.9% Sodium Chloride injection; Solution for injection/infusion (placebo)
Modality
Other

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