RATIONALE: Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This randomized phase II trial is studying giving sorafenib tosylate together with everolimus to see how well it works compared with sorafenib tosylate alone in treating patients with localized, unresectable, or metastatic liver cancer.
OBJECTIVES: * To determine if sorafenib tosylate with versus without everolimus can stop tumor progression in patients with localized, unresectable, or metastatic hepatocellular carcinoma. * To evaluate changes in symptom-related and global quality of life (QL) and QL benefit over the course of trial treatment in these patients. * To compare the primary endpoint (i.e., progression-free survival at week 12) to the QL benefit within 12 weeks from baseline. * To evaluate how symptom-related and global QL indicators map on the single summary index derived from a standardized measure of health status for utility cost analysis. OUTLINE: This is a multicenter study. Patients are stratified according to WHO performance status (0 vs 1), disease spread (extrahepatic spread vs non-extrahepatic spread), and center. Patients are randomized to 1 of 2 treatment arms. * Arm A (standard treatment): Patients receive oral sorafenib tosylate twice daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. * Arm B (investigational treatment): Patients receive oral sorafenib tosylate twice daily and oral everolimus once daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Some patients may undergo CT scan or MRI at baseline and at 6 and 12 weeks during study to assess tumor response, tumor size, and tumor density. Patients complete quality of life questionnaires at baseline and every 2 weeks for 12 weeks during study treatment. After completion of study treatment, patients are followed every 2 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
106
Sorafenib 2 x 400 mg daily plus everolimus 1 x 5 mg daily
Sorafenib 2 x 400 mg daily
Medizinische Universität Wien
Vienna, Austria
Szent Laszlo Korhaz
Budapest, Hungary
Saint Claraspital AG
Basel, Switzerland
Progression-free survival
Time frame: at 12 weeks
Objective response
Time frame: during trial treatment and follow-up (max. 3 years)
Disease stabilization (DS)
Time frame: under trial treatment
Duration of disease stabilization
Time frame: Duration of DS (CR, PR or SD) will be calculated from the time that measurement criteria are met for the first time until documented tumor progression.
Progression-free survival (PFS)
Time frame: PFS will be calculated from randomization until documented tumor progression or death, whichever occurs first
Time to progression (TTP)
Time frame: TTP will be calculated from randomization until documented tumor progression or tumor-related death
Overall survival
Time frame: from randomization until death
Adverse events at baseline and during trial treatment
Time frame: All AEs will be assessed according to NCI CTCAE v3.0.
Serum alpha fetoprotein (AFP) level
Time frame: Serum AFP levels will be measured during the therapy, if AFP is ≥ 1.5 x ULN at baseline.
Viral reactivation in patients with chronic hepatitis B or C virus infection
Time frame: Number of patients with HCV/HBV (re)-activation during trial treatment
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Clinical Cancer Research Center at University Hospital Basel
Basel, Switzerland
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland
Inselspital Bern
Bern, Switzerland
Kantonsspital Bruderholz
Bruderholz, Switzerland
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
Kantonsspital Liestal
Liestal, Switzerland
...and 5 more locations
Correlation between vitamin B12 and overall survival
Time frame: The baseline vitamin B12 value, collected at trial randomization, is correlated to overall survival when dichotomized by the cut-point of 600 ng/L.