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Hepatocellular CarcinomaPhase 2PRODIGE 21NCT01357486

Palliative Treatment of Hepatocellular Carcinoma in Patient With CHILD B Cirrhosis

A Phase 2 study testing sorafenib, Pravastatin and Sorafenib + Pravastatin in people with Hepatocellular Carcinoma and CHILD B, run by University Hospital, Bordeaux at 35 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma, CHILD B
What is being tested?
sorafenib, Pravastatin and Sorafenib + Pravastatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
35 sitesFrance
Study dates
14 Nov 2011to 12 Apr 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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.

Trial locations and contacts

35 sites in 1 country.

35 sites in 1 country

France35 sites

  • CH d'Abbeville

    Abbeville, 80142

  • CH Pays d'Aix

    Aix-en-Provence, 13616

  • CH d'Auxerre

    Auxerre, 89011

  • CH de la Côte Basque

    Bayonne, 64109

  • CH de Béziers

    Béziers, 34525

  • AP-HP- Hôpital Jean-Verdier

    Bondy, 93143

  • CHU de Bordeaux

    Bordeaux, 33075

  • CH Duchenne

    Boulogne-sur-Mer, 62321

  • AP-HP Hôpital Henri Mondor

    Créteil, 94010

  • CHU Le Bocage

    Dijon, 21079

  • CH Départemental Vendée

    La Roche-sur-Yon, 85925

  • CH Le Mans

    Le Mans, 72037

  • CH de Bretagne Sud

    Lorient, 56100

  • Hôpital privé Jean Mermoz

    Lyon, 69008

  • AP-HM Hôpital de la Timone

    Marseille, 13385

  • CH de Meaux

    Meaux, 77104

  • CH Mont de Marsan

    Mont-de-Marsan, 40024

  • CHU de Nancy Hôpital Brabois

    Nancy, 54511

  • CHU de Nantes Hôpital de l'Hotel Dieu

    Nantes, 44093

  • CHU Nîmes

    Nîmes, 30029

  • CHR d'Orléans - Hôpital La Source

    Orléans, 45067

  • Groupe Hospitalier Paris Saint Joseph

    Paris, 75014

  • CH Perpignan

    Perpignan, 66046

  • CHU de Bordeaux, Hôpital du Haut Lévèque

    Pessac, 33604

  • CH de la Région d'Annecy

    Pringy, 74374

  • Centre Eugène Marquis

    Rennes, 35042

  • Clinique Mathilde

    Rouen, 76000

  • Clinique Armoricaine de Radiologie

    Saint-Brieuc, 22015

  • Centre René Gauducheau CLCC Nantes Atlantique

    Saint-Herblain, 44805

  • CH Gaston Ramon

    Sens, 89100

  • CH Saint-Malo

    St-Malo, 35400

  • Centre Régional de Lutte contre le Cancer Centre Paul Strauss

    Strasbourg, 67065

  • Hôpitaux Universitaires de Strasbourg Hôpital civil

    Strasbourg, 67091

  • Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre

    Strasbourg, 67098

  • CHRU de Tours

    Tours, 37044

Other trials in France

About this study

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

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).

Read the 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.

Being tested
sorafenib, Pravastatin, Sorafenib + Pravastatin, patients receiving best supportive care
Keywords
Hepatocellular Carcinoma, CHILD B, palliative management, Sorafenib, Pravastatin
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sorafenibDrug

    patients receiving sorafenib 400 mg - twice a day

  • PravastatinDrug

    patients receiving pravastatin 40 mg - once a day

  • Sorafenib + PravastatinDrug

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

  • patients receiving best supportive careOther

    palliative management

Study groups in NCT01357486
Study groupRoleWhat they receive
AExperimentalpatients receiving sorafenib 400 mg - twice a day
Receives: Drug: sorafenib
BExperimentalpatients receiving pravastatin 40 mg - once a day
Receives: Drug: Pravastatin
CExperimentalpatients receiving sorafenib 400 mg (twice a day) and pravastatin 40 mg (once a day)
Receives: Drug: Sorafenib + Pravastatin
DOtherpatients receiving best supportive care
Receives: Other: patients receiving best supportive care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to radiologic progression

    Measured: 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)

  1. Overall survival

    Measured: End of the study (estimated date August 2012)

  2. Survival without progression

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

  3. Time to treatment failure

    Measured: 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)

  4. Objective response rate at four months

    Measured: Radiological evaluation at 4 months

  5. Number and description of AE for toxicity and SAE

    Measured: Clinical evaluation every month

  6. Quality of life

    Measured: Clinical evaluation every month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2011 (estimated)
  2. Study start14 Nov 2011
  3. Primary completion12 Apr 2017
  4. Study completion12 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01357486
Sponsor's protocol ID
CHUBX 2010/22
Acronym
PRODIGE 21
Status last verified
Apr 2017
First submitted
13 May 2011
Last updated
1 May 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18650514

  • 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.

    PubMed 16935385

  • 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.

    PubMed 11286466

  • 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.

    PubMed 15239254

  • 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.

    PubMed 16581333

  • 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.

    PubMed 18477802

  • 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.

    PubMed 33420951

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sorafenib, Pravastatin and Sorafenib + Pravastatin in people with Hepatocellular Carcinoma and CHILD B, run by University Hospital, Bordeaux at 35 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01357486, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2017.

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