Efficacy and Safety Study of Sorafenib Plus Pravastatin to Treat Advanced Hepatocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the overall survival (OS) in order to assess the efficacy and safety of pravastatin as adjuvant treatment to sorafenib.

Official Title
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Phase-II, Multicenter, Randomized, Double-Blind, Parallel-Group Trial to Compare the Efficacy and Safety of Sorafenib Plus Pravastatin Against Sorafenib Plus Placebo in Patients With Advanced Hepatocarcinoma

Conditions
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Advanced Hepatocarcinoma

Intervention / Treatment
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* Drug: Pravastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been diagnosed with advanced hepatocarcinoma (HCC), confirmed histologically or with non-invasive criteria, according to the clinical practice guidelines by the American Association for the Study of Liver Diseases (AASLD) during a maximum period of 15 days prior to the baseline visit. Males and females, over 18 years of age. Patients who have not previously received treatment with sorafenib. Have an ECOG ≤ 2. Liver function: Child A and B7. Life expectancy greater than 12 weeks. Adequate kidney function: serum creatinine concentration less than or equal to 1.5 times the upper limit of normal (ULN). Sign the written informed consent before starting any procedure, including randomization. Exclusion Criteria: Patients who routinely (more than 3 times a week) take some sort of statin. Patients with hypersensitivity to statins. Pregnant or breastfeeding women. Peripheral neuropathy: grade 2 or higher Patients who have been diagnosed, within the previous 5 years, with another type of tumor, except for non-melanoma skin cancer, or in situ carcinoma of the cervix or the urinary bladder. Patients receiving chemotherapy or radiotherapy for another type of tumor. Patients with heart failure greater than NYHA grade II, hypertension that is uncontrolled with medication, uncontrolled arrhythmias or AMI within the previous six months. A history of perforation or hemorrhage due to a gastroduodenal ulcus within the last month. Greater hemorrhagic diseases. Asthmatic patients uncontrolled with medication. Any other contraindication associated to the use of statins. Physical or psychological inability to participate in the trial. Treatment with another investigational drug or participation in another clinical trial within 6 months prior to inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sorafenib plus Pravastatin<br>The treatment received will be sorafenib 400 mg/12 h + pravastatin 40 mg/24 h. | Drug: Pravastatin<br>* Treatment: Patients will be randomized in two groups, A and B: Control Group (A ≡ 1): Patients will receive treatment with sorafenib 400 mg/12 h + placebo/24 h. Experimental Group (B ≡ 2): The treatment received will be sorafenib 400 mg/12 h + pravastatin 40 mg/24 h.<br>|
| Placebo Comparator: Sorafenib plus Placebo<br>The treatment received will be sorafenib 400 mg/12 h + placebo/24 h. | Drug: Pravastatin<br>* Treatment: Patients will be randomized in two groups, A and B: Control Group (A ≡ 1): Patients will receive treatment with sorafenib 400 mg/12 h + placebo/24 h. Experimental Group (B ≡ 2): The treatment received will be sorafenib 400 mg/12 h + pravastatin 40 mg/24 h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | To evaluate the overall survival (OS) in order to assess the efficacy and safety of pravastatin as adjuvant treatment to sorafenib. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | To evaluate the time to progression (TTP). | 18 months | 
| time to symptomatic progression (TTSP). | To evaluate the time to symptomatic progression (TTSP). | 18 months |