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Palliative Treatment of Hepatocellular Carcinoma in Patient With CHILD B Cirrhosis (PRODIGE 21)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Federation Francophone de Cancerologie Digestive
UNICANCER
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01357486
First received: May 13, 2011
Last updated: June 22, 2016
Last verified: June 2016
  Purpose
The incidence of Hepatocellular Carcinoma (HCC) is currently increasing in Europe and in France and about 2 / 3 of patients, are not eligible for curative treatment at the time of diagnosis. The palliative management of patients with advanced and symptomatic disease is complex and requires treatment combining anti-tumor activity and safety in patients with impaired liver functions. Sorafenib is the standard of care in a palliative setting, but the benefit of sorafenib in patient with altered liver function is uncertain. The aim of this trial is to study the interest of sorafenib in patients with HCC and impaired liver function compared to pravastatin (a drug with anti-tumoral activity in HCC) or to the combination sorafenib/pravastatin or to best supportive care (usually used in these patients).

Condition Intervention Phase
Hepatocellular Carcinoma
CHILD B
Drug: sorafenib
Drug: Pravastatin
Drug: Sorafenib + Pravastatin
Other: patients receiving best supportive care
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial Evaluating the Administration of Sorafenib or Pravastatin or Association Sorafenib-pravastatin or Best Supportive Care for the Palliative Treatment of Hepatocellular Carcinoma in Patient With CHILD B Cirrhosis

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Time to radiologic progression [ Time Frame: Every 4 weeks (CT-scan or MRI) until progression of HCC or date of last news (for patients alive or dead without progression) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: End of the study (estimated date August 2012) ] [ Designated as safety issue: Yes ]
  • Survival without progression [ Time Frame: Every 4 weeks (CT-scan or MRI) until progression of HCC or date of last news (for patients alive or dead without progression) ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: every 4 weeks (CT-scan or MRI) until clinical or radiological progression of HCC or date of last news (for patients alive or dead without progression) ] [ Designated as safety issue: No ]
  • Objective response rate at four months [ Time Frame: Radiological evaluation at 4 months ] [ Designated as safety issue: No ]
  • Number and description of AE for toxicity and SAE [ Time Frame: Clinical evaluation every month ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Clinical evaluation every month ] [ Designated as safety issue: Yes ]

Enrollment: 160
Study Start Date: November 2011
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
patients receiving sorafenib 400 mg - twice a day
Drug: sorafenib
patients receiving sorafenib 400 mg - twice a day
Experimental: B
patients receiving pravastatin 40 mg - once a day
Drug: Pravastatin
patients receiving pravastatin 40 mg - once a day
Experimental: C
patients receiving sorafenib 400 mg (twice a day) and pravastatin 40 mg (once a day)
Drug: Sorafenib + Pravastatin
patients receiving sorafenib 400 mg (twice a day) and pravastatin 40 mg (once a day)
D
patients receiving best supportive care
Other: patients receiving best supportive care
palliative management

Detailed Description:

The incidence of Hepatocellular Carcinoma (HCC) is currently increasing in Europe and in France. It almost always occurs on liver disease and in 80 to 90% of cases, at least in France, on liver with cirrhosis. If curative treatment may be proposed for some "small" HCC (transplantation, resection, percutaneous destruction), about 2 / 3 of patients, which represents nearly 4,000 new cases per year in France, are not eligible for such treatment. The palliative management of patients with advanced and symptomatic disease is complex and requires treatment combining anti-tumor activity and safety in patients with impaired liver functions. Indeed, in most cases the palliative treatment of HCC is applied to patients with altered liver function (stage B of the Child-Pugh classification).

To date, the proposed treatment in France for such patients is based on best supportive care.

The objective of this study is to assess the interest in this situation of 2 molecules - taken alone or in combination:

  • Sorafenib, the reference in the palliative treatment of advanced hepatocellular carcinoma (Stage C of the BCLC classification). Yet the safety and efficacy of sorafenib in patients with altered liver function (CHILD B) are not clearly defined and its use remains discouraged by French recommendations in these patients.
  • Pravastatin whose interest in the palliative treatment of HCC was suggested by several phase II studies with a good safety profile in cirrhotic patients.

In this French multicenter open randomized study, 160 patients will be included in 4 arms (40/arms): sorafenib, pravastatin, pravastatin + sorafenib, and supportive care.

The aim of this phase II multicenter study is to select the two best arms for further Phase III study in order to identify a reference treatment in this palliative situation.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Male and female subjects > 18 years age

- Hepatocellular carcinoma histologically diagnosed or in case of inability to perform a histology by non invasive radiological criteria in presence of known cirrhosis: (i) Hepatic lesion measuring between 1 and 2 cm in diameter : CT-scan + MRI (eventually an Ultrasound contrast) : HCC diagnosed with contrast uptake in the arterial phase and rapid wash out in the venous /late phase on two imaging techniques.

(ii)Hepatic lesion with a diameter > 2 cm : CT-scan or MRI +alpha fetoprotein : HCC diagnosed with contrast uptake in the arterial phase and a rapid wash out in the venous /late phase or a alpha fetoprotein > 200µg/L

  • Patient not eligible for curative treatment (transplantation, resection, destruction or percutaneous chemo-embolization) or HCC still evolving after failure of a specific treatment
  • Score CHILD B
  • ECOG performance status 0/1/2
  • Score BCLC B or C
  • Adequate haematologic function with haemoglobin > 8 g/dl, platelet count > 50000x 109/L, absolute neutrophil count > 1000 / mm3
  • Creatinine < 2 times the upper limit of normal
  • Written informed consent

Exclusion Criteria:

  • Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study
  • Pregnancy
  • Myocardial infarction less than 6 months, uncontrolled hypertension, congestive heart failure(NYHA class > 2) , anti- arrhythmic treatment other than beta-blockers or digoxin
  • Digestive bleeding within 30 days before inclusion
  • Hepatic transplantation
  • Patients receiving or having received a statine for less than 6 months before HCC diagnostic
  • Prior use of sorafenib
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Previous or concurrent cancer, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumor. Any cancer curatively treated > 5 years prior to entry is permitted
  • Known or suspected history of allergy to sorafenib or pravastatin.
  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: NCT01357486

Locations
France
CH d'Abbeville
Abbeville, France, 80142
CH Pays d'Aix
Aix-en-provence, France, 13616
CH d'Auxerre
Auxerre, France, 89011
CH de la Côte Basque
Bayonne, France, 64109
AP-HP- Hôpital Jean-Verdier
Bondy, France, 93143
CHU de Bordeaux
Bordeaux, France, 33075
CH Duchenne
Boulogne Sur Mer, France, 62321
CH de Béziers
Béziers, France, 34525
AP-HP Hôpital Henri Mondor
Creteil, France, 94010
CHU Le Bocage
Dijon, France, 21079
CH Départemental Vendée
La Roche-sur-yon, France, 85925
CH Le Mans
Le Mans, France, 72037
CH de Bretagne Sud
Lorient, France, 56100
Hôpital privé Jean Mermoz
Lyon, France, 69008
AP-HM Hôpital de la Timone
Marseille, France, 13385
CH de Meaux
Meaux, France, 77104
CH Mont de Marsan
Mont-de-marsan, France, 40024
CHU de Nancy Hôpital Brabois
Nancy, France, 54511
CHU de Nantes Hôpital de l'Hotel Dieu
Nantes, France, 44093
CHU Nîmes
Nimes, France, 30029
CHR d'Orléans - Hôpital La Source
Orleans, France, 45067
Groupe Hospitalier Paris Saint Joseph
Paris, France, 75014
CH Perpignan
Perpignan, France, 66046
CHU de Bordeaux, Hôpital du Haut Lévèque
Pessac, France, 33604
CH de la Région d'Annecy
Pringy, France, 74374
Centre Eugène Marquis
Rennes, France, 35042
Clinique Mathilde
Rouen, France, 76000
Clinique Armoricaine de Radiologie
Saint Brieuc, France, 22015
CH Saint-Malo
Saint Malo, France, 35400
Centre René Gauducheau CLCC Nantes Atlantique
Saint-herblain, France, 44805
CH Gaston Ramon
Sens, France, 89100
Centre Régional de Lutte contre le Cancer Centre Paul Strauss
Strasbourg, France, 67065
Hôpitaux Universitaires de Strasbourg Hôpital civil
Strasbourg, France, 67091
Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre
Strasbourg, France, 67098
CHRU de Tours
Tours, France, 37044
Sponsors and Collaborators
University Hospital, Bordeaux
Federation Francophone de Cancerologie Digestive
UNICANCER
Investigators
Principal Investigator: Jean-Frédéric BLANC, MD-PhD University Hospital, Bordeaux
  More Information

Publications:

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01357486     History of Changes
Other Study ID Numbers: CHUBX 2010/22 
Study First Received: May 13, 2011
Last Updated: June 22, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Hepatocellular Carcinoma
CHILD B
palliative management
Sorafenib
Pravastatin

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Fibrosis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pathologic Processes
Pravastatin
Sorafenib
Niacinamide
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 26, 2016