Palliative Treatment of Hepatocellular Carcinoma in Patient With CHILD B Cirrhosis

NCT01357486 | Completed Phase 2 DMC

• 1 other identifier: CHUBX 2010/22
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 35

Brief Summary

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).

Conditions

Hepatocellular Carcinoma; CHILD B

Keywords

Hepatocellular Carcinoma; CHILD B; palliative management; Sorafenib; Pravastatin

Outcome Measures

Primary Outcomes (1)

• Time to radiologic progression

  Every 4 weeks (CT-scan or MRI) until progression of HCC or date of last news (for patients alive or dead without progression)

Secondary Outcomes (6)

• Overall survival

  End of the study (estimated date August 2012)

• Survival without progression

  Every 4 weeks (CT-scan or MRI) until progression of HCC or date of last news (for patients alive or dead without progression)

• Time to treatment failure

  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)

• Objective response rate at four months

  Radiological evaluation at 4 months

• Number and description of AE for toxicity and SAE

  Clinical evaluation every month

Study Arms (4)

A

EXPERIMENTAL

patients receiving sorafenib 400 mg - twice a day

Drug: sorafenib

B

EXPERIMENTAL

patients receiving pravastatin 40 mg - once a day

Drug: Pravastatin

C

EXPERIMENTAL

patients receiving sorafenib 400 mg (twice a day) and pravastatin 40 mg (once a day)

Drug: Sorafenib + Pravastatin

D

OTHER

patients receiving best supportive care

Other: patients receiving best supportive care

Interventions

sorafenib DRUG

patients receiving sorafenib 400 mg - twice a day

A

Pravastatin DRUG

patients receiving pravastatin 40 mg - once a day

B

Sorafenib + Pravastatin DRUG

patients receiving sorafenib 400 mg (twice a day) and pravastatin 40 mg (once a day)

C

patients receiving best supportive care OTHER

palliative management

D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Federation Francophone de Cancerologie Digestive: collaborator
• UNICANCER: collaborator

Study Sites (35)

CH d'Abbeville

Abbeville, 80142, France

Location

CH Pays d'Aix

Aix-en-Provence, 13616, France

Location

CH d'Auxerre

Auxerre, 89011, France

Location

CH de la Côte Basque

Bayonne, 64109, France

Location

CH de Béziers

Béziers, 34525, France

Location

AP-HP- Hôpital Jean-Verdier

Bondy, 93143, France

Location

CHU de Bordeaux

Bordeaux, 33075, France

Location

CH Duchenne

Boulogne-sur-Mer, 62321, France

Location

AP-HP Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU Le Bocage

Dijon, 21079, France

Location

CH Départemental Vendée

La Roche-sur-Yon, 85925, France

Location

CH Le Mans

Le Mans, 72037, France

Location

CH de Bretagne Sud

Lorient, 56100, France

Location

Hôpital privé Jean Mermoz

Lyon, 69008, France

Location

AP-HM Hôpital de la Timone

Marseille, 13385, France

Location

CH de Meaux

Meaux, 77104, France

Location

CH Mont de Marsan

Mont-de-Marsan, 40024, France

Location

CHU de Nancy Hôpital Brabois

Nancy, 54511, France

Location

CHU de Nantes Hôpital de l'Hotel Dieu

Nantes, 44093, France

Location

CHU Nîmes

Nîmes, 30029, France

Location

CHR d'Orléans - Hôpital La Source

Orléans, 45067, France

Location

Groupe Hospitalier Paris Saint Joseph

Paris, 75014, France

Location

CH Perpignan

Perpignan, 66046, France

Location

CHU de Bordeaux, Hôpital du Haut Lévèque

Pessac, 33604, France

Location

CH de la Région d'Annecy

Pringy, 74374, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Clinique Mathilde

Rouen, 76000, France

Location

Clinique Armoricaine de Radiologie

Saint-Brieuc, 22015, France

Location

Centre René Gauducheau CLCC Nantes Atlantique

Saint-Herblain, 44805, France

Location

CH Gaston Ramon

Sens, 89100, France

Location

CH Saint-Malo

St-Malo, 35400, France

Location

Centre Régional de Lutte contre le Cancer Centre Paul Strauss

Strasbourg, 67065, France

Location

Hôpitaux Universitaires de Strasbourg Hôpital civil

Strasbourg, 67091, France

Location

Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre

Strasbourg, 67098, France

Location

CHRU de Tours

Tours, 37044, France

Location

Related Publications (7)

• Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

  PMID: 18650514 BACKGROUND

• Taras D, Blanc JF, Rullier A, Dugot-Senant N, Laurendeau I, Vidaud M, Rosenbaum J. Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity. J Hepatol. 2007 Jan;46(1):69-76. doi: 10.1016/j.jhep.2006.06.015. Epub 2006 Jul 28.

  PMID: 16935385 BACKGROUND

• Kawata S, Yamasaki E, Nagase T, Inui Y, Ito N, Matsuda Y, Inada M, Tamura S, Noda S, Imai Y, Matsuzawa Y. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer. 2001 Apr 6;84(7):886-91. doi: 10.1054/bjoc.2000.1716.

  PMID: 11286466 BACKGROUND

• Lersch C, Schmelz R, Erdmann J, Hollweck R, Schulte-Frohlinde E, Eckel F, Nader M, Schusdziarra V. Treatment of HCC with pravastatin, octreotide, or gemcitabine--a critical evaluation. Hepatogastroenterology. 2004 Jul-Aug;51(58):1099-103.

  PMID: 15239254 BACKGROUND

• Cohen DE, Anania FA, Chalasani N; National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol. 2006 Apr 17;97(8A):77C-81C. doi: 10.1016/j.amjcard.2005.12.014. Epub 2006 Feb 3.

  PMID: 16581333 BACKGROUND

• Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.

  PMID: 18477802 BACKGROUND

• Blanc JF, Khemissa F, Bronowicki JP, Monterymard C, Perarnau JM, Bourgeois V, Obled S, Abdelghani MB, Mabile-Archambeaud I, Faroux R, Seitz JF, Locher C, Senellart H, Villing AL, Audemar F, Costentin C, Deplanque G, Manfredi S, Edeline J; PRODIGE 21 collaborators. Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis. Hepatol Int. 2021 Feb;15(1):93-104. doi: 10.1007/s12072-020-10120-3. Epub 2021 Jan 9.

  PMID: 33420951 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; Pravastatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Jean-Frédéric BLANC, MD-PhD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2011
• First Posted: May 20, 2011
• Study Start: November 14, 2011
• Primary Completion: April 12, 2017
• Study Completion: April 12, 2017
• Last Updated: May 1, 2017

Record last verified: 2017-04

Locations

FR (35)