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

Sponsor

Federation Francophone de Cancerologie Digestive (Other)

Overall Status

Completed

CT.gov ID

NCT01075555

Collaborator

Centre Hospitalier Universitaire Dijon (Other)

323

Enrollment

Location

Arms

Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer	Drug: pravastatin sodium Drug: sorafenib tosylate	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

323 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2010

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: sorafenib sorafenib	Drug: sorafenib tosylate
Experimental: sorafenib + pravastatine sorafenib + pravastatine	Drug: pravastatin sodium Drug: sorafenib tosylate

Arm

Intervention/Treatment

Active Comparator: sorafenib

sorafenib

Drug: sorafenib tosylate

Experimental: sorafenib + pravastatine

sorafenib + pravastatine

Drug: pravastatin sodium

Drug: sorafenib tosylate

Outcome Measures

Primary Outcome Measures

Overall survival [2014]

Secondary Outcome Measures

Progression-free survival [2014]
Time to progression [2014]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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