Randomized Phase III Trial Sorafenib-Pravastatin Versus Sorafenib Alone for the Palliative Treatment of Child-Pugh A Hepatocellular Carcinoma
18 Years
N/A
Both
Liver Cancer
Trial Information
Randomized Phase III Trial Sorafenib-Pravastatin Versus Sorafenib Alone for the Palliative Treatment of Child-Pugh A Hepatocellular Carcinoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Safety Issue:
No
Principal Investigator
Jean-Louis Jouve
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hopital Du Bocage
Authority:
Unspecified
Study ID:
CDR0000666232
NCT ID:
NCT01075555
Start Date:
February 2010
Completion Date:
Related Keywords:
- Liver Cancer
- adult primary hepatocellular carcinoma
- localized unresectable adult primary liver cancer
- advanced adult primary liver cancer
- recurrent adult primary liver cancer
- Liver Neoplasms
- Carcinoma, Hepatocellular
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