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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by BioAlliance Pharma SA
Sponsor:
Information provided by (Responsible Party):
BioAlliance Pharma SA
ClinicalTrials.gov Identifier:
NCT01655693
First received: July 26, 2012
Last updated: August 7, 2014
Last verified: August 2014
  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 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.


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Doxorubicin
Drug: Best Standard of Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicentre, 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 Standard of Care (BSC) in Patients With Advanced Hepatocellular Carcinoma (HCC) After Failure or Intolerance to Sorafenib. ReLive Study.

Resource links provided by NLM:


Further study details as provided by BioAlliance Pharma SA:

Primary Outcome Measures:
  • Overall 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.


Secondary Outcome Measures:
  • Incidence 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: No ]
    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.


Estimated Enrollment: 390
Study Start Date: June 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 unacceptable toxicity
Drug: Doxorubicin
Other Name: Doxorubicin Transdrug (DT) at 20mg/m2
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 unacceptable toxicity
Drug: Doxorubicin
Other Name: Doxorubicin Transdrug (DT) at 30mg/m2
Active Comparator: Best Standard of Care
Patients randomized in the control group will receive treatment according to the investigator's choice, until disease progression or unacceptable toxicity
Drug: Best Standard of Care

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Patients with porta hepatis lymph nodes, extrahepatic metastases, or portal/suprahepatic vein thrombosis without extension in inferior/superior vena cava, are eligible;
  • HCC diagnosed according to the AASLD and/or 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);
  • 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 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;
  • HIV infection;
  • Risk of variceal bleeding;
  • 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 NYHA classification), recent (< 6 months) acute coronary syndrome, clinically significant ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655693

Contacts
Contact: Berangere Vasseur, MD +33 (0)1 45 58 76 04 berangere.vasseur@bioalliancepharma.com

  Show 52 Study Locations
Sponsors and Collaborators
BioAlliance Pharma SA
Investigators
Principal Investigator: Philippe Merle, MD Croix-Rousse Hospital - Lyon-France
  More Information

No publications provided

Responsible Party: BioAlliance Pharma SA
ClinicalTrials.gov Identifier: NCT01655693     History of Changes
Other Study ID Numbers: BA2011/03/04, 2011-002843-92
Study First Received: July 26, 2012
Last Updated: August 7, 2014
Health Authority: France: Committee for the Protection of Personnes
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Belgium: Ethics Committee
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Austria: Ethikkommission
Austria: Austrian Medicines and Medical Devices Agency
Hungary: Institutional Ethics Committee
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Comité Ético de Investigación Clínica
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by BioAlliance Pharma SA:
Intermediate/advanced hepatocellular carcinoma
After failure or intolerance to Sorafenib.

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014