Sorafenib Tosylate With or Without Everolimus in Treating Patients With Localized, Unresectable, or Metastatic Liver Cancer
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Sorafenib Alone or in Combination With Everolimus in Patients With Unresectable Hepatocellular Carcinoma. A Randomized Multicenter Phase II Trial.|
- Progression-free survival [ Time Frame: at 12 weeks ] [ Designated as safety issue: No ]
- Objective response [ Time Frame: during trial treatment and follow-up (max. 3 years) ] [ Designated as safety issue: No ]
- Disease stabilization (DS) [ Time Frame: under trial treatment ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]
- Progression-free survival (PFS) [ Time Frame: PFS will be calculated from randomization until documented tumor progression or death, whichever occurs first ] [ Designated as safety issue: No ]
- Time to progression (TTP) [ Time Frame: TTP will be calculated from randomization until documented tumor progression or tumor-related death ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: from randomization until death ] [ Designated as safety issue: No ]
- Adverse events at baseline and during trial treatment [ Time Frame: All AEs will be assessed according to NCI CTCAE v3.0. ] [ Designated as safety issue: Yes ]
- 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. ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]
|Study Start Date:||November 2009|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm A: Sorafenib standard
• Arm A (standard treatment): Sorafenib 2 x 400 mg daily until progressive disease, unacceptable toxicity, or consent withdrawal. (46 patients).
Drug: sorafenib tosylate
Sorafenib 2 x 400 mg daily
Other Name: BAY 43-9006
Experimental: Arm B: Sorafenib + everolimus
• Arm B (investigational treatment): Sorafenib 2 x 400 mg daily plus everolimus 1 x 5 mg daily until progressive disease, unacceptable toxicity, or consent withdrawal. (60 patients)
Sorafenib 2 x 400 mg daily plus everolimus 1 x 5 mg daily
Other Name: RAD001Drug: sorafenib tosylate
Sorafenib 2 x 400 mg daily
Other Name: BAY 43-9006
- 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.
|Medizinische Universität Wien|
|Wien, Austria, 1090|
|Szent Laszlo Korhaz|
|Budapest, Hungary, 1097|
|Clinical Cancer Research Center at University Hospital Basel|
|Basel, Switzerland, CH-4031|
|Saint Claraspital AG|
|Basel, Switzerland, CH-4016|
|Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli|
|Bellinzona, Switzerland, 6500|
|Bern, Switzerland, CH-3010|
|Bruderholz, Switzerland, CH-4101|
|Hopital Cantonal Universitaire de Geneve|
|Geneva, Switzerland, CH-1211|
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Switzerland, CH-1011|
|Liestal, Switzerland, CH-4410|
|CHCVS - Hôpital de Sion|
|Sion, Switzerland, 1950|
|Kantonsspital - St. Gallen|
|St. Gallen, Switzerland, CH-9007|
|Thun, Switzerland, 3600|
|City Hospital Triemli|
|Zurich, Switzerland, CH-8063|
|Zurich, Switzerland, CH-8091|
|Study Chair:||Dieter Koeberle, MD||Cantonal Hospital of St. Gallen|
|Study Chair:||Jean-Francois Dufour, MD||University Hospital Inselspital, Berne|
|Study Chair:||Gyorgy Bodoky, MD, PhD||Szent Laszlo Korhaz|
|Study Chair:||Michael Montemurro, MD||CHUV Lausanne|