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

Study Overview
=================
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.

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

Conditions
-----------------
Liver Cancer

Intervention / Treatment
-----------------
* Drug: pravastatin sodium
* Drug: sorafenib tosylate


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sorafenib<br>sorafenib | Drug: sorafenib tosylate<br> <br> |
| Experimental: sorafenib + pravastatine<br>sorafenib + pravastatine | Drug: pravastatin sodium<br> <br> Drug: sorafenib tosylate<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2014 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 2014 | 
| Time to progression |  | 2014 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer