Efficacy and Safety Study of Sorafenib Plus Pravastatin to Treat Advanced Hepatocarcinoma (ESTAHEP-2010)

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Hepatocarcinoma
• Intervention / Treatment: Drug: Pravastatin

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Gipuzkoa
    • San Sebastian, Gipuzkoa, Spain, 20014
      • Hospital Donostia, Instituto Biodonostia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sorafenib plus Pravastatin; The treatment received will be sorafenib 400 mg/12 h + pravastatin 40 mg/24 h.	Drug: Pravastatin; 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.
Placebo Comparator: Sorafenib plus Placebo; The treatment received will be sorafenib 400 mg/12 h + placebo/24 h.	Drug: Pravastatin; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Donostia
• Collaborators: INSTITUTO BIODONOSTIA
• Investigators: Study Chair: Juan I Arenas, MD,PHD, Hospital Donostia; Principal Investigator: Javier Bustamante Scheneider, MD, Hospital De Cruces; Principal Investigator: Trinidad Serrano Aullo, MD, PHD, Hospital Clinico Universitario Lozano Blesa; Principal Investigator: Mercedes Iñarrairaegui Bastarrica, MD, Clinica Universitaria de Navarra; Principal Investigator: Sonia Blanco Sampascual, MD, Hospital de Basurto; Principal Investigator: Maria Varela, MD, PHD, Hospital Central de Asturias; Principal Investigator: Oscar Nuñez, MD, Hospital Infanta Sofia

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: August 15, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (Estimate): August 17, 2011

Study Record Updates

• Last Update Posted (Actual): September 20, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin
• Other Study ID Numbers: ESTAHEP-2010; 2010-024421-21 (EudraCT Number)