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

Overview[ - collapse ][ - ]

Purpose 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 supportive 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.
ConditionCarcinoma, Hepatocellular
InterventionDrug: Doxorubicin
Drug: Doxorubicin
Drug: Best Supportive Care
PhasePhase 3
SponsorBioAlliance Pharma SA
Responsible PartyBioAlliance Pharma SA
ClinicalTrials.gov IdentifierNCT01655693
First ReceivedJuly 26, 2012
Last UpdatedMay 3, 2013
Last verifiedMay 2013

Tracking Information[ + expand ][ + ]

First Received DateJuly 26, 2012
Last Updated DateMay 3, 2013
Start DateJune 2012
Estimated Primary Completion DateDecember 2014
Current Primary Outcome MeasuresOverall survival(OS) in each group [Time Frame: at 1 year (expected average)] [Designated as safety issue: No]Survival status will be collected at each visit (at least every 2 weeks) during the study treatment period and then every 3 months until death for an expected average of 1 year.
Current Secondary Outcome MeasuresIncidence and severity of all Treatment Emergent Adverse Events according to NCI-CTC v4.0 scale in each groups [Time Frame: until 2 months after last treatment intake] [Designated as safety issue: Yes]Adverse events will be collected at each visit (at least every 2 weeks) during the study treatment period, and then 2 months after the last treatment intake for an expected average of 6 months.

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy and Safety Doxorubicin Transdrug Study in Patients Suffering From Advanced Hepatocellular Carcinoma
Official TitleMulticentre, Randomised, Controlled, Open-label Study Comparing the Efficacy and Safety of Slow Repeated IV Infusions of 2 Doses of Doxorubicin Transdrug™ (DT) (20mg/m2 and 30mg/m2) to Those of Best Supportive Care (BSC) in Patients Suffering From Advanced Hepatocellular Carcinoma (HCC) After Failure or Intolerance to Sorafenib. ReLive Study
Brief 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. Only those who can not benefit from treatment
for which efficacy is demonstrated are eligible.

These patients are usually proposed either best supportive 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.
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.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionCarcinoma, Hepatocellular
InterventionDrug: Doxorubicin
Other Names:
Doxorubicin Transdrug (DT) at 20mg/m2Drug: Doxorubicin
Other Names:
Doxorubicin Transdrug (DT) at 30mg/m2Drug: Best Supportive Care
Study Arm (s)
  • Experimental: Doxorubicin Transdrug (DT) at 20mg/m2
    DT 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 toxicity
  • Experimental: Doxorubicin Transdrug (DT) at 30 mg/m2
    DT 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 toxicity
  • Active Comparator: Best Supportive Care
    Patients randomized in the control group will receive treatment according to the investigator's choice, until disease progression or toxicity

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment390
Estimated Completion DateDecember 2014
Estimated Primary Completion DateJune 2014
Eligibility Criteria
Inclusion Criteria:

- 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

- HCC diagnosed according to the AASLD criteria:

- Cyto-histology criteria and/or Non-invasive criteria

- Without cirrhosis or with a non decompensated cirrhosis (Child-Pugh score from A5 to
B7 included);

- ECOG Performance Status 0 or 1;

- Laboratory tests as follows:

- Platelets ≥ 50,000 /mm3

- Neutrophil count ≥ 1000/mm3

- Hemoglobin ≥ 10g/dL

- Serum transaminases < 5 ULN (NCI/CTC grades 0, 1, or 2)

- Alkaline phosphatases < 5 ULN (NCI/CTC grades 0, 1, or 2)

- Serum bilirubin < 35 µM/L (or 2.0 mg/dL);

- Signed and dated written informed consent form.

Exclusion Criteria:

- 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 can
be included);

- HCC developed on transplanted liver;

- HIV infection;

- Risk of variceal bleeding;

- SaO2 < 95%;

- Presence of a significant acute or chronic respiratory disease, pleural effusion;

- Presence of recent (< 6 months) or current cardiac failure (class III or IV NYHA
classification), recent (< 6 months) acute coronary syndrome, clinically significant
ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke,
MI…);

- Patients having undergone a 450 mg/m² cumulated dose of doxorubicin;

- Patients currently treated with immunosuppressive agents that cannot be stopped;

- Patients with unstable ongoing medical/surgical problems;

- Patients with a life expectancy of less than 2 months;

- Patients who had participated in another clinical trial in the last 30 days;

- Women of child-bearing age who are unwilling or unable to use an effective
contraception method during the study treatment period and for 2 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 2 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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Berangere Vasseur, MD
+33 (0)1 45 58 76 04
berangere.vasseur@bioalliancepharma.com
Location CountriesFrance

Administrative Information[ + expand ][ + ]

NCT Number NCT01655693
Other Study ID NumbersBA2011/03/04
Has Data Monitoring CommitteeYes
Information Provided ByBioAlliance Pharma SA
Study SponsorBioAlliance Pharma SA
CollaboratorsNot Provided
Investigators Principal Investigator: Philippe Merle, MD Croix-Rousse Hospital - Lyon-France
Verification DateMay 2013

Locations[ + expand ][ + ]

Hospital Amiens
Amiens, France, 80054
Principal Investigator: Eric Nguyen-Khac, MD
Recruiting
CHU
Angers, France
Principal Investigator: Paul CALES, MD
Not yet recruiting
Hospital jean Minjoz
Besançon, France, 25000
Principal Investigator: Vincent Di Martino
Recruiting
Hospital Saint André
Bordeaux, France, 33075
Principal Investigator: Jean-Frédérique Blanc, MD
Recruiting
CHU
Caen, France
Principal Investigator: Isabelle OLLIVIER-HOURMAND, MD
Not yet recruiting
Hospital Estaing
Clermont-Ferrand, France, 63003
Principal Investigator: Armand Abergel, MD
Recruiting
Hospital Henri-Mondor
Creteil, France, 94010
Principal Investigator: Charlotte Costentin, MD
Not yet recruiting
Centre Inter-Communal
Creteil, France
Principal Investigator: Isabelle ROSA, MD
Not yet recruiting
CHU
Dijon, France
Contact: Patrick HILLON, MD
Principal Investigator: Patrick HILLON, MD
Not yet recruiting
Hospital Grenoble
La Tronche, France, 38700
Principal Investigator: Jean-Pierre Zarski, MD
Recruiting
CHU Dupuytren
Limoges, France
Principal Investigator: Nicole TUBIANA-MATHIEU, MD
Not yet recruiting
Hospital Croix Rousse
Lyon, France, 69317
Principal Investigator: Philippe Merle, MD
Recruiting
Hospital La Conception
Marseille, France, 13005
Principal Investigator: Santandrea Gerolami, MD
Recruiting
Hospital Saint Eloi
Montpellier, France, 34295
Principal Investigator: Georges-Philippe Pageaux, MD
Recruiting
Hospital Brabois
Nancy, France, 54511
Principal Investigator: Jean Pierre Bronowicki, MD
Recruiting
Hospital Hotel Dieu
Nantes, France, 44093
Principal Investigator: Yann Touchefeu, MD
Recruiting
CHU - Hôpital Archet
Nice, France
Principal Investigator: Albert TRAN, MD
Not yet recruiting
Hospital La Source
Orleans, France, 45067
Principal Investigator: Barbara Dauvois, MD
Not yet recruiting
Hospital Pitié-Salpetriere
Paris, France, 75013
Principal Investigator: Vlad Ratziu, MD
Recruiting
Hospital Tenon
Paris, France, 75020
Principal Investigator: Jean-Didier Grange, MD
Not yet recruiting
Hôpital Saint-Antoine
Paris, France
Principal Investigator: Olivier ROSMORDUC, MD
Not yet recruiting
HEGP
Paris, France
Principal Investigator: Julien TAIEB, MD
Not yet recruiting
Hospital Saint Jean
Perpignan, France, 66046
Principal Investigator: Faiza Khemissa-Akouz, MD
Recruiting
Hospital Lyon Sud
Pierre Benite, France, 69495
Principal Investigator: Driffa Moussata, MD
Not yet recruiting
IC LOIRE
Saint-Etienne, France
Contact: Jean-Marc PHELIP, MD
Principal Investigator: Jean-Marc PHELIP, MD
Recruiting
Hospital Civil
Strasbourg, France, 67091
Principal Investigator: Michel Doffoel, MD
Recruiting
Hospital Paul Brousse
Villejuif, France, 94804
Principal Investigator: Gilles Pelletier, MD
Recruiting