Sorafenib alone or in combination with everolimus in patients with unresectable hepatocellular carcinoma. A randomized multicenter phase II trial.

• Conditions: Patients with unresectable hepatocellular carcinoma.

• Registration Number: EUCTR2009-011884-35-HU
• Lead Sponsor: Swiss Group for Clinical Cancer Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

Histologically, cytologically or radiologically confirmed diagnosis of HCC, localized but surgically unresectable or metastatic.
HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC) staging classification.
Child-Pugh class A or mildly decompensated Child-Pugh class B liver dysfunction.
Measurable disease: spiral/multi-slice CT/MRI according to revised RECIST 1.1.
WHO performance status 0-1.
Adequate hematological values: hemoglobin = 90 g/L, neutrophils = 1.5 x 109/L, platelets = 75 x 109/L.
Adequate renal function: creatinine clearance = 40 mL/min.
Adequate hepatic function: ALT = 5 x upper limit of normal (ULN).
Adequate coagulation parameter: INR = 2.
Urine dipstick for proteinuria = 1+ or protein in spot urine sample < 0.6 g/L.
Age = 18 years.
Women are not breastfeeding, are using effective contraception if sexually active, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. A negative pregnancy test is mandatory for all women < 50 years (unless considered unnecessary by the investigator). Men agree not to father a child during participation in the trial and during the 12 months thereafter.
Patient compliance and geographic proximity allow proper staging and follow-up.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Prior systemic anti-cancer treatment for HCC.
Treatment with estrogen containing supplementary therapy.
Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
Prior organ transplantation.
Patients with locally advanced disease who are candidates for radical surgery.
Known fibrolamellar HCC or mixed cholangiocarcinoma/HCC.
History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months.
Documented variceal hemorrhage within 3 months before randomization.
Requirement of anticoagulant therapy except for low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis (DVT).
History (within last six months) or presence of clinically significant acute or unstable cardiovascular, cerebrovascular, renal, gastrointestinal, pulmonary, endocrine, central nervous system or immunological disorders (with the exception of the presence of hepatitis B virus (HBV), HCV hepatitis, or cirrhosis).
Clinical symptoms or history of CNS metastases or leptomeningeal disease (no imaging required).
Encephalopathy.
Known HIV infection.
Active infection requiring i.v. antibiotics at randomization.
Arterial hypertension = 150/100 mmHg despite therapy.
Ongoing cardiac dysrhythmias of NCI CTCAE grade = 2, or atrial fibrillation of any grade, prolongation of QTc > 500 msec in screening electrocardiogram (ECG) or history of familial long QT syndrome.
Repeated paracentesis (more than 1 per month).
Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization.
Chronic treatment with systemic steroids or another immunosuppressive agent.
Current use or anticipated need for drugs that are known CYP3A4 inhibitors or inducers (for a comprehensive list see http://medicine.iupui.edu/clinpharm/ddis/), unless the drugs are medically necessary and no substitutes are available.
Inability to take oral medications.
Psychiatric disorder precluding understanding of information of trial-related topics, giving informed consent or interfering with compliance for oral drug intake

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Investigate if the combination of sorafenib plus everolimus can stop tumor progression, with a sorafenib monotherapy group used to control selection bias. No formal comparison is planned.;Secondary Objective: Quality of life, tumor density.;Primary end point(s): Progression free at 12 weeks.<br>Objective response. <br>Disease stabilization (DS).<br>Duration of DS.<br>Progression free survival (PFS).<br>Time to progression (TTP).<br>Overall survival (OS).<br>Adverse events (AEs).<br>Serum alpha fetoprotein (AFP) level.<br>Viral (re)-activation in patients with chronic hepatitis B/C virus infection.<br>Vitamin B12 effect on OS.