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

March 27, 2020 updated by: Federation Francophone de Cancerologie Digestive

Randomized Phase III Trial Sorafenib-Pravastatin Versus Sorafenib Alone for the Palliative Treatment of Child-Pugh A Hepatocellular Carcinoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

323

Phase

  • Phase 3

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
      • Dijon, France, 21000
        • Hôpital du Bocage

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of hepatocellular carcinoma (HCC), meeting 1 of the following criteria:

    • Histologically confirmed HCC

    • If histological proof can not be obtained (e.g., ascites, coagulation disorders), the diagnosis may be made in cases of cirrhosis according to the 2005 EASL/AASLD criteria by demonstration of a focal hepatic lesion > 10 mm, meeting 1 of the following criteria:

      • Hypervascular tumor < 2 cm by 2 dynamic-imaging techniques (e.g., spiral CT scan, MRI scan, or ultrasound with contrast medium)
      • Hypervascular tumor ≥ 2 cm by 1 dynamic-imaging technique (e.g., spiral CT scan, MRI scan, or ultrasound with contrast medium)
  • No progressive disease following prior treatment
  • Not eligible for curative treatment (i.e., transplantation, resection, or percutaneous destruction) or chemoembolization
  • 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

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
Active Comparator: sorafenib
Drug: sorafenib tosylate
Experimental: sorafenib + pravastatine
Drug: sorafenib tosylate
Drug: pravastatin sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 2014
2014

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 2014
2014
Time to progression
Time Frame: 2014
2014

Collaborators and Investigators

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

Sponsor

Federation Francophone de Cancerologie Digestive

Collaborators

Centre Hospitalier Universitaire Dijon

Investigators

  • Principal Investigator: Jean-Louis Jouve, Hôpital du Bocage
  • Principal Investigator: Jacques Denis, MD, Hopital Louise Michel

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

February 1, 2010

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

February 24, 2010

First Submitted That Met QC Criteria

February 24, 2010

First Posted (Estimate)

February 25, 2010

Study Record Updates

Last Update Posted (Actual)

March 30, 2020

Last Update Submitted That Met QC Criteria

March 27, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000666232
  • FFCD-PRODIGE-11
  • FFCD-0803
  • EUDRACT-2009-015785-64
  • EU-21005

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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