Sorafenib Alone or in Combination With Everolimus in Patients With Unresectable Hepatocellular Carcinoma. A Randomized Multicenter Phase II Trial.
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 106
- Locations
- 15
- Primary Endpoint
- Progression-free survival
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A: Sorafenib standard
• Arm A (standard treatment): Sorafenib 2 x 400 mg daily until progressive disease, unacceptable toxicity, or consent withdrawal. (46 patients).
Intervention: sorafenib tosylate (Drug)
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)
Intervention: everolimus (Drug)
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)
Intervention: sorafenib tosylate (Drug)
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: at 12 weeks
Secondary Outcomes
- Viral reactivation in patients with chronic hepatitis B or C virus infection(Number of patients with HCV/HBV (re)-activation during trial treatment)
- Overall survival(from randomization until death)
- Serum alpha fetoprotein (AFP) level(Serum AFP levels will be measured during the therapy, if AFP is ≥ 1.5 x ULN at baseline.)
- Objective response(during trial treatment and follow-up (max. 3 years))
- Disease stabilization (DS)(under trial treatment)
- Adverse events at baseline and during trial treatment(All AEs will be assessed according to NCI CTCAE v3.0.)
- Progression-free survival (PFS)(PFS will be calculated from randomization until documented tumor progression or death, whichever occurs first)
- Correlation between vitamin B12 and overall survival(The baseline vitamin B12 value, collected at trial randomization, is correlated to overall survival when dichotomized by the cut-point of 600 ng/L.)
- Time to progression (TTP)(TTP will be calculated from randomization until documented tumor progression or tumor-related death)
- Duration of disease stabilization(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.)