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Carcinoma, HepatocellularPhase 3ReLiveNCT01655693

Efficacy and Safety Doxorubicin Transdrug Study in Patients Suffering From Advanced Hepatocellular Carcinoma

A Phase 3 study testing Doxorubicin 20 mg/m2 and Doxorubicin 30 mg/m2 in people with Carcinoma, Hepatocellular, run by Valerio Therapeutics at 70 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this phase III study is to determine whether Doxorubicin Transdrug (DT) is effective in the treatment of patients suffering from advanced Hepatocellular Carcinoma (HCC) after failure or intolerance to Sorafenib. Patients with HCC with or without cirrhosis and with good liver functions are eligible. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Doxorubicin 20 mg/m2 and Doxorubicin 30 mg/m2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
397 participants
Where
70 sitesin 11 countries
Study dates
Jun 2012to May 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or non-pregnant, non-breast feeding female;
  • Aged ≥ 18 years;
  • Patient with:
  • advanced HCC (BCLC-C according to BCLC staging classification) having progressed under Sorafenib therapy or intolerant to Sorafenib, or;
  • intermediate HCC (BCLC-B) non eligible or non responders to transarterial chemoembolization (TACE), and having progressed under or intolerant to Sorafenib therapy
  • Patients with porta hepatis lymph nodes, extrahepatic metastases, or portal/suprahepatic vein thrombosis without extension in inferior/superior vena cava, are eligible;
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  • HCC diagnosed according to the American Association for Study of Liver Diseases (AASLD) and/or European Association for the Study of the Liver (EASL) criteria:
  • Radiological Criteria applicable in cirrhotic liver:
  • Nodule ≥ 10 mm: one imaging technique among MRI and CT-scan showing typical appearances for HCC defined as arterial enhancement and rapid washout in portal venous or delayed phase;
  • If appearance not typical for HCC on initial imaging: second contrast enhanced study (CT or MRI) showing typical appearances for HCC defined as arterial enhancement and rapid wash-out in portal venous or delayed phase;
  • And/Or cyto-histology criteria (e.g. in case of atypical lesions for HCC at imaging, absence of cirrhosis);
  • Without cirrhosis or with a non decompensated cirrhosis (Child-Pugh score from A5 to B7 included);
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
  • Laboratory tests as follows:
  • Platelets ≥ 50,000 /mm3
  • Neutrophil count ≥ 1000/mm3
  • Hemoglobin ≥ 10g/dL
  • Serum transaminases < 5 upper limit normal (ULN) (NCI/common toxicity criteria (CTC) grades 0, 1, or 2)
  • Alkaline phosphatases < 5 ULN (NCI/CTC grades 0, 1, or 2)
  • Serum bilirubin < 35 micromolar (µM)/L (or 2.0 mg/dL);
  • Signed and dated written informed consent form.

Who cannot join

  • Cirrhosis with a Child-Pugh score B8-C15;
  • Untreated chronic hepatitis B;
  • Patients eligible for curative treatments (transplantation, surgical resection, percutaneous treatment);
  • Patients eligible for palliative treatments with demonstrated efficacy: TACE, Sorafenib; Patients who failed to Sorafenib treatment or intolerant to sorafenib are eligible and can be included if Sorafenib has been stopped at least 2 weeks before randomization;
  • Prior history of malignancy with the exception of adequately treated basal cell carcinoma or in situ cervical cancer in complete remission since five years at least;
  • HCC developed on transplanted liver;
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  • HIV infection;
  • Risk of variceal bleeding;
  • Oxygen saturation (SaO2) < 95%;
  • Presence of a significant acute or chronic respiratory disease defined as NCI/CTCAE > grade 2;
  • Presence of recent (< 6 months) or current cardiac failure (class III or IV New York Heart Association (NYHA) classification), recent (< 6 months) acute coronary syndrome, clinically significant ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke, myocardial infarction (MI)…);
  • Prior cumulative dose of 300 mg/m² of doxorubicin or equivalent;
  • Patients currently treated with immunosuppressive agents that cannot be stopped;
  • Patients whose medical or surgical conditions are unstable and may not allow the study completion or compliance, and specially patients with uncontrolled diabetes;
  • Uncontrolled systemic infection;
  • Patients with a life expectancy of less than 2 months;
  • Patients who have received an experimental drug in another clinical trial in the last 30 days prior to randomization in the present clinical trial;
  • Women of child-bearing age who are unwilling or unable to use an effective contraception method during the study treatment period and for 6 months after the last administration of study drug, and their male partner(s) refusing to use a condom (if applicable);
  • Men who are unwilling or unable to use a condom during the study treatment period and for 6 months after the last administration of study drug, and their female partner(s) refusing to use one of the appropriate effective contraception methods (if applicable);
  • Patients unwilling or unable to comply with protocol requirements and scheduled visits.

Trial locations and contacts

70 sites in 11 countries.

70 sites in 11 countries

France25 sites

  • Hospital Amiens

    Amiens, 80054

  • Hospital Jean Minjoz

    Besançon, 25000

  • Hospital Saint André

    Bordeaux, 33075

  • Centre hospitalier P Oudot

    Bourgoin, 38302

  • Hospital Estaing

    Clermont-Ferrand, 63003

  • Centre Hospitalier Beaujon

    Clichy, 92110

  • Hospital Henri-Mondor

    Créteil, 94010

  • Centre Jean-François Leclerc

    Dijon, 21079

  • CHU

    Dijon

  • Hospital Grenoble

    La Tronche, 38700

  • CHU Dupuytren

    Limoges, 87042

  • Hospital Croix Rousse

    Lyon, 69317

  • Hospital La Timone

    Marseille, 13005

  • Hospital Saint Eloi

    Montpellier, 34295

  • Hospital Brabois

    Nancy, 54511

  • Hospital Hotel Dieu

    Nantes, 44093

  • CHU - Hôpital Archet

    Nice

  • Hospital La Source

    Orléans, 45067

  • Hospital Pitié-Salpetriere

    Paris, 75013

  • Hospital Tenon

    Paris, 75020

  • Hospital Saint Jean

    Perpignan, 66046

  • CHU de Rouen- Hôpital Charles Nicolle

    Rouen, 76031

  • IC LOIRE

    Saint-Etienne

  • Hospital Civil

    Strasbourg, 67091

  • Hospital Paul Brousse

    Villejuif, 94804

Other trials in France

Spain10 sites

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Hospital Universitario Virgen de la Arrixaca

    El Palmar Murcia, 30120

  • Complejo Hospitalario de Jaen

    Jaén, 23006

  • Hospital General Universario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Universitario Madrid Sanchinarro

    Madrid, 28050

  • Hospital Carlos Haya

    Málaga, 29010

  • Hospital Universario Son Espaces

    Palma de Mallorca, 07010

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

  • Hospital Universitario Río Hortega

    Valladolid, 47012

Other trials in Spain

Italy8 sites

  • Irccs Centro Di Riferimento Oncologico (Cro)

    Aviano, 33081

  • Ospedale Civile e degli Infermi

    Faenza, 48018

  • Ausl 12 Livorno Ospedale Unico della Versilia

    Lido di Camaiore, 55041

  • IRST Istituto Romagnolo Ricerca e Cura dei Tumori

    Meldola, 47014

  • Granda Osp. Magg. Policlinico

    Milan, 20122

  • Azienda Ospedaliera Policlinico di Modena

    Modena, 41124

  • A.O. Ospedale Maggiore della Carità

    Novara, 28100

  • Study site

    Rimini, 47900

Other trials in Italy

Egypt6 sites

  • Medical Oncology department /Mansoura University Hospitals

    Al Mansurah, 35516

  • Clinical Research Center/ Alexandria university hospital

    Alexandria

  • Oncology Department, Medical Research Institute, Alexandria University

    Alexandria

  • Medical Oncology department /Ain Shams University Hospitals

    Cairo

  • National hepatology and tropical medicine research institute

    Cairo

  • National Liver Institute / Menoufyia University

    Menofia, 32700

Other trials in Egypt

Germany5 sites

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Halle (Saale)

    Halle, 06120

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universität Leipzig AöR

    Leipzig, 04103

  • Klinikum rechts der Isar der TU Munchen II

    München, 81675

Other trials in Germany

Belgium4 sites

  • CHU Brugmann

    Brussels, 1020

  • UCL Saint-Luc

    Brussels, 1200

  • CHU Sart Tilman

    Liège, 4000

  • CHU UCL Mont-Godinne Dinant

    Yvoir

Other trials in Belgium

Hungary4 sites

  • Semmelweis Egyetem Radiológiai és Onkoterápiás Klinika

    Budapest, 1082

  • Egyesített Szent István és Szent László Kórház - Rendelőintézet

    Budapest, 1097

  • Debreceni Egyetem Orvos- és Egészségtudományi Centrum Onkológiai Intézet

    Debrecen, 4032

  • Szegedi Tudományegyetem Onkoterápiás Klinika

    Szeged, 6720

Other trials in Hungary

United States3 sites

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Penn State Hershey Cancer Institute

    Hershey, Pennsylvania, 17033

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

Other trials in United States

Austria2 sites

  • Krankenhaus der Elisabethinen Linz GmbH

    Linz, 4020

  • Medical University Vienna

    Vienna, 1090

Other trials in Austria

Turkey (Türkiye)2 sites

  • Hacettepe University Medical Faculty

    Ankara

  • Ege Univeristy Medical Faculty,

    Izmir

Other trials in Turkey (Türkiye)

Lebanon1 site

  • Ain Wazein Hospital

    El Chouf

Other trials in Lebanon

About this study

Official title: Multicentre, Randomised, Controlled, Open-label Study Comparing the Efficacy and Safety of Doxorubicin Transdrug™ to Best Standard of Care in Patients With Advanced Hepatocellular Carcinoma. ReLive Study.

The purpose of this phase III study is to determine whether Doxorubicin Transdrug (DT) is effective in the treatment of patients suffering from advanced Hepatocellular Carcinoma (HCC) after failure or intolerance to Sorafenib. Patients with HCC with or without cirrhosis and with good liver functions are eligible. Only those who can not benefit from treatment for which efficacy is demonstrated are eligible.

These patients are usually proposed either best standard of care (BSC) or participation to clinical trials. Patients eligible for the RELIVE study will receive either DT at 20 mg/m2 or DT at 30 mg/m2 or the BSC.

Read the detailed description

Doxorubicin-Transdrug™ (DT) is a nanoparticle formulation of doxorubicin.In in vitro and in vivo models, DT was shown to overcome the multidrug resistance (MDR) and to be more effective than doxorubicin on both sensitive and resistant tumour models and in particular in the X/myc bi-transgenic MDR murine model of HCC.

Being tested
Doxorubicin 20 mg/m2, Doxorubicin 30 mg/m2, Best Standard of Care
Keywords
Intermediate/advanced hepatocellular carcinoma, After failure or intolerance to Sorafenib.
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Doxorubicin 20 mg/m2Drug

    Also called Doxorubicin Transdrug (DT) at 20 mg/m2

  • Doxorubicin 30 mg/m2Drug

    Also called Doxorubicin Transdrug (DT) at 30 mg/m2

  • Best Standard of CareDrug

    Also called BSC

Study groups in NCT01655693
Study groupRoleWhat they receive
Doxorubicin Transdrug (DT) at 20 mg/m2ExperimentalDT will be infused over 6 hours through the intravenous (IV) route at dose of 20 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity
Receives: Drug: Doxorubicin 20 mg/m2
Doxorubicin Transdrug (DT) at 30 mg/m2ExperimentalDT will be infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity
Receives: Drug: Doxorubicin 30 mg/m2
Best Standard of CareActive comparatorPatients randomized in the control group will receive treatment according to the investigator's choice, until disease progression or unacceptable toxicity
Receives: Drug: Best Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    OS is defined as the time from date of randomization to the date of death from any cause.

    Measured: Time from date of randomization to the date of death from any cause with initial assessment up to 24 months and follow-up assessment up to 45 months.

Secondary outcomes (2)

  1. Progression-free Survival (PFS)

    PFS is defined as time from the date of randomisation to the date of the first documented progression or death from any cause. PFS determined by independent radiological review according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 is determine by at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression.

    Measured: Time from date of randomization to date of first documented progression or death from any cause, which ever came first, assessed up to 20 months.

  2. Objective Response Rate (ORR)

    ORR is defined as percent of patients whose best overall response is complete response (CR) or partial response (PR) during the study treatment period and based on the evaluation of independent radiological review according to RECIST 1.1 for target lesions and assessed by MRI: CR is disappearance of all targets extra nodal lesions and the regression of all nodal lesions to < 10 mm; PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. PD is at least a 20% increase in the sum of diameters of target lesions, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression.

    Measured: Time from date of first treatment cycle to date of last cycle of treatment for the full duration of study treatment up to 24 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionMay 2017
  4. Study completionMay 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
397 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01655693
Sponsor's protocol ID
BA2011/03/04
Other IDs
2011-002843-92
Acronym
ReLive
Status last verified
May 2021
First submitted
26 Jul 2012
Last updated
2 Jun 2021
Data monitoring committee
Yes

Publications

  • Merle P, Blanc JF, Phelip JM, Pelletier G, Bronowicki JP, Touchefeu Y, Pageaux G, Gerolami R, Habersetzer F, Nguyen-Khac E, Casadei-Gardini A, Borbath I, Tran A, Wege H, Saad AS, Colombo M, Abergel A, Richou C, Waked I, Yee NS, Mole A, Attali P, Le Boulicaut J, Vasseur B; RELIVE Investigators. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jun;4(6):454-465. doi: 10.1016/S2468-1253(19)30040-8. Epub 2019 Apr 4.

    PubMed 30954567

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Doxorubicin 20 mg/m2 and Doxorubicin 30 mg/m2 in people with Carcinoma, Hepatocellular, run by Valerio Therapeutics at 70 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in France, Spain, Italy, Egypt, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Time from date of randomization to the date of death from any cause with initial assessment up to 24 months and follow-up assessment up to 45 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01655693, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.

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