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

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT01357486

Collaborator

Federation Francophone de Cancerologie Digestive (Other), UNICANCER (Other)

160

Enrollment

Locations

Arms

64.9

Actual Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

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

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 Design

Study Type:

Interventional

Actual Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Actual Study Start Date :

Nov 14, 2011

Actual Primary Completion Date :

Apr 12, 2017

Actual Study Completion Date :

Apr 12, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
Quality of life [Clinical evaluation every month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	CH d'Abbeville	Abbeville	France	80142
2	CH Pays d'Aix	Aix-en-provence	France	13616
3	CH d'Auxerre	Auxerre	France	89011
4	CH de la Côte Basque	Bayonne	France	64109
5	AP-HP- Hôpital Jean-Verdier	Bondy	France	93143
6	CHU de Bordeaux	Bordeaux	France	33075
7	CH Duchenne	Boulogne Sur Mer	France	62321
8	CH de Béziers	Béziers	France	34525
9	AP-HP Hôpital Henri Mondor	Creteil	France	94010
10	CHU Le Bocage	Dijon	France	21079
11	CH Départemental Vendée	La Roche-sur-yon	France	85925
12	CH Le Mans	Le Mans	France	72037
13	CH de Bretagne Sud	Lorient	France	56100
14	Hôpital privé Jean Mermoz	Lyon	France	69008
15	AP-HM Hôpital de la Timone	Marseille	France	13385
16	CH de Meaux	Meaux	France	77104
17	CH Mont de Marsan	Mont-de-marsan	France	40024
18	CHU de Nancy Hôpital Brabois	Nancy	France	54511
19	CHU de Nantes Hôpital de l'Hotel Dieu	Nantes	France	44093
20	CHU Nîmes	Nimes	France	30029
21	CHR d'Orléans - Hôpital La Source	Orleans	France	45067
22	Groupe Hospitalier Paris Saint Joseph	Paris	France	75014
23	CH Perpignan	Perpignan	France	66046
24	CHU de Bordeaux, Hôpital du Haut Lévèque	Pessac	France	33604
25	CH de la Région d'Annecy	Pringy	France	74374
26	Centre Eugène Marquis	Rennes	France	35042
27	Clinique Mathilde	Rouen	France	76000
28	Clinique Armoricaine de Radiologie	Saint Brieuc	France	22015
29	CH Saint-Malo	Saint Malo	France	35400
30	Centre René Gauducheau CLCC Nantes Atlantique	Saint-herblain	France	44805
31	CH Gaston Ramon	Sens	France	89100
32	Centre Régional de Lutte contre le Cancer Centre Paul Strauss	Strasbourg	France	67065
33	Hôpitaux Universitaires de Strasbourg Hôpital civil	Strasbourg	France	67091
34	Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre	Strasbourg	France	67098
35	CHRU de Tours	Tours	France	37044