Sorafenib Tosylate With or Without Pravastatin in Treating Patients With Liver Cancer and Cirrhosis - Full Text View

Sponsor:	Federation Francophone de Cancerologie Digestive
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01075555

Purpose

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.

Condition	Intervention	Phase
Liver Cancer	Drug: pravastatin sodium Drug: sorafenib tosylate Other: laboratory biomarker analysis Other: pharmacogenomic studies Procedure: quality-of-life assessment	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Phase III Trial Sorafenib-Pravastatin Versus Sorafenib Alone for the Palliative Treatment of Child-Pugh A Hepatocellular Carcinoma

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cancer Cirrhosis Liver Cancer

Drug Information available for: Pravastatin Pravastatin sodium Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	474
Study Start Date:	February 2010
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01075555

Locations

France
Hopital Du Bocage	Recruiting
Dijon, France, 21000
Contact: Contact Person 33-3-8029-3750

Sponsors and Collaborators

Federation Francophone de Cancerologie Digestive

Investigators

Principal Investigator:	Jean-Louis Jouve	Hopital Du Bocage
Principal Investigator:	Jacques Denis, MD	Hopital Louise Michel

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT01075555 History of Changes
Other Study ID Numbers:	CDR0000666232, FFCD-PRODIGE-11, FFCD-0803, EUDRACT-2009-015785-64, EU-21005
Study First Received:	February 24, 2010
Last Updated:	November 4, 2010
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer

Additional relevant MeSH terms:

Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pravastatin

Sorafenib
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 24, 2012