Sorafenib Tosylate With or Without Pravastatin in Treating Patients With Liver Cancer and Cirrhosis

NCT ID: NCT01075555

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 323 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2015-09-30

Brief Summary

RATIONALE: Sorafenib tosylate and pravastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of liver cancer by blocking blood flow to the tumor. It is not yet known whether sorafenib tosylate is more effective when given alone or together with pravastatin in treating patients with liver cancer and cirrhosis.

PURPOSE: This randomized phase III trial is studying sorafenib tosylate given together with pravastatin to see how well it works compared with giving sorafenib tosylate alone in treating patients with liver cancer and cirrhosis.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the effects of sorafenib tosylate and pravastatin versus sorafenib tosylate alone on overall survival of patients with hepatocellular carcinoma and Child-Pugh Class A cirrhosis.

Secondary

• To evaluate the effect of this regimen on progression-free survival, time to progression, time to treatment failure, and quality of life (QLQ-C30 and FACT hep) in these patients.
• To evaluate the benefit of on-site monitoring versus the centralized data management monitoring of these patients.
• To characterize polymorphisms to specify the haplotype diversity in these patients.
• To test both diagnostic and prognostic signatures by quantitative RT-PCR to determine if they can predict response to these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, Cancer of the Liver Italian Program (CLIP) score (0 vs 1 vs 2-4), WHO performance status (0 vs 1 vs 2), portal vein thrombosis (presence vs absence), and extrahepatic metastases (presence vs absence). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral sorafenib tosylate twice daily on days 1-28 and oral pravastatin once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaires (QLQ-C30 and FACT) at baseline and then every 4 weeks during and after completion of study therapy.

Blood and tissue samples may be collected for laboratory analysis, including pharmacogenomic studies.

After completion of study therapy, patients are followed up periodically.

Conditions

Liver Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sorafenib

sorafenib

Group Type: ACTIVE_COMPARATOR

sorafenib tosylate

Intervention Type: DRUG

sorafenib + pravastatine

sorafenib + pravastatine

Group Type: EXPERIMENTAL

pravastatin sodium

Intervention Type: DRUG

sorafenib tosylate

Intervention Type: DRUG

Interventions

pravastatin sodium

Intervention Type: DRUG

sorafenib tosylate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Cancer of the Liver Italian Program (CLIP) prognosis score 0 to 4
• Child-Pugh score A
• No extrahepatic disease threatening the short- or medium-term vital prognosis

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy > 12 weeks
• Transaminases ≤ 5 times upper limit of normal (ULN)
• Serum creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after completion of study therapy
• No other cancerous pathology, except for carcinoma in situ of the cervix, superficial bladder tumors, treated basal cell carcinoma, or any other cancer treated curatively ≥ 3 years ago
• No cardiac insufficiency (NYHA class II or IV congestive heart failure), arterial hypertension, uncontrolled arrhythmia, or myocardial infarction within the past 6 months
• No digestive hemorrhage within the past month
• No major bleeding disorder

PRIOR CONCURRENT THERAPY:

• No prior or other concurrent statins
• No prior sorafenib tosylate

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: collaborator

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Louis Jouve

Role: PRINCIPAL_INVESTIGATOR

Hopital Du Bocage

Jacques Denis, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Louise Michel

Locations

Hopital Du Bocage

Dijon, , France

Countries

France

References

Jouve JL, Lecomte T, Bouche O, Barbier E, Khemissa Akouz F, Riachi G, Nguyen Khac E, Ollivier-Hourmand I, Debette-Gratien M, Faroux R, Villing AL, Vergniol J, Ramee JF, Bronowicki JP, Seitz JF, Legoux JL, Denis J, Manfredi S, Phelip JM; PRODIGE-11 investigators/collaborators. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma. J Hepatol. 2019 Sep;71(3):516-522. doi: 10.1016/j.jhep.2019.04.021. Epub 2019 May 22.

Reference Type: BACKGROUND

PMID: 31125576 (View on PubMed)

Other Identifiers

FFCD-PRODIGE-11

Identifier Type: -

Identifier Source: secondary_id

FFCD-0803

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-015785-64

Identifier Type: -

Identifier Source: secondary_id

EU-21005

Identifier Type: -

Identifier Source: secondary_id

CDR0000666232

Identifier Type: -

Identifier Source: org_study_id