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

April 28, 2017 updated by: University Hospital, Bordeaux

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Abbeville, France, 80142
        • CH d'Abbeville
      • Aix-en-provence, France, 13616
        • Ch Pays D'Aix
      • Auxerre, France, 89011
        • CH d'Auxerre
      • Bayonne, France, 64109
        • CH de la Côte Basque
      • Bondy, France, 93143
        • AP-HP- Hôpital Jean-Verdier
      • Bordeaux, France, 33075
        • CHU de Bordeaux
      • Boulogne Sur Mer, France, 62321
        • CH Duchenne
      • Béziers, France, 34525
        • CH de Béziers
      • Creteil, France, 94010
        • AP-HP Hôpital Henri Mondor
      • Dijon, France, 21079
        • CHU Le Bocage
      • La Roche-sur-yon, France, 85925
        • CH Départemental Vendée
      • Le Mans, France, 72037
        • CH Le Mans
      • Lorient, France, 56100
        • CH de Bretagne Sud
      • Lyon, France, 69008
        • Hopital Prive Jean Mermoz
      • Marseille, France, 13385
        • AP-HM Hopital de la Timone
      • Meaux, France, 77104
        • CH de Meaux
      • Mont-de-marsan, France, 40024
        • CH Mont de Marsan
      • Nancy, France, 54511
        • CHU de Nancy Hôpital Brabois
      • Nantes, France, 44093
        • CHU de Nantes Hopital de l'Hotel Dieu
      • Nimes, France, 30029
        • Chu Nimes
      • Orleans, France, 45067
        • CHR d'Orléans - Hôpital La Source
      • Paris, France, 75014
        • Groupe hospitalier Paris saint Joseph
      • Perpignan, France, 66046
        • Ch Perpignan
      • Pessac, France, 33604
        • CHU de Bordeaux, Hopital du Haut Leveque
      • Pringy, France, 74374
        • CH de la Region d'Annecy
      • Rennes, France, 35042
        • Centre Eugene Marquis
      • Rouen, France, 76000
        • Clinique Mathilde
      • Saint Brieuc, France, 22015
        • Clinique Armoricaine de Radiologie
      • Saint Malo, France, 35400
        • CH Saint-Malo
      • Saint-herblain, France, 44805
        • Centre René Gauducheau CLCC Nantes Atlantique
      • Sens, France, 89100
        • CH Gaston Ramon
      • Strasbourg, France, 67091
        • Hôpitaux Universitaires de Strasbourg Hôpital Civil
      • Strasbourg, France, 67065
        • Centre Régional de Lutte contre le Cancer Centre Paul Strauss
      • Strasbourg, France, 67098
        • Hopitaux Universitaires de Strasbourg, Hopital Hautepierre
      • Tours, France, 37044
        • CHRU De Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)
Other: D
patients receiving best supportive care
Other: patients receiving best supportive care
palliative management

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: End of the study (estimated date August 2012)
End of the study (estimated date August 2012)
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)
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
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)
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
Time Frame: Radiological evaluation at 4 months
Radiological evaluation at 4 months
Number and description of AE for toxicity and SAE
Time Frame: Clinical evaluation every month
Clinical evaluation every month
Quality of life
Time Frame: Clinical evaluation every month
Clinical evaluation every month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Collaborators

Federation Francophone de Cancerologie Digestive
UNICANCER

Investigators

  • Principal Investigator: Jean-Frédéric BLANC, MD-PhD, University Hospital, Bordeaux

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2011

Primary Completion (Actual)

April 12, 2017

Study Completion (Actual)

April 12, 2017

Study Registration Dates

First Submitted

May 13, 2011

First Submitted That Met QC Criteria

May 18, 2011

First Posted (Estimate)

May 20, 2011

Study Record Updates

Last Update Posted (Actual)

May 1, 2017

Last Update Submitted That Met QC Criteria

April 28, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2010/22

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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