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Sorafenib Tosylate With or Without Everolimus in Treating Patients With Localized, Unresectable, or Metastatic Liver Cancer

Phase 2
Completed
Conditions
Liver Cancer
Interventions
Registration Number
NCT01005199
Lead Sponsor
Swiss Group for Clinical Cancer Research
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
106
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm B: Sorafenib + everolimussorafenib tosylate• 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)
Arm A: Sorafenib standardsorafenib tosylate• Arm A (standard treatment): Sorafenib 2 x 400 mg daily until progressive disease, unacceptable toxicity, or consent withdrawal. (46 patients).
Arm B: Sorafenib + everolimuseverolimus• 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)
Primary Outcome Measures
NameTimeMethod
Progression-free survivalat 12 weeks
Secondary Outcome Measures
NameTimeMethod
Viral reactivation in patients with chronic hepatitis B or C virus infectionNumber of patients with HCV/HBV (re)-activation during trial treatment
Overall survivalfrom randomization until death
Serum alpha fetoprotein (AFP) levelSerum AFP levels will be measured during the therapy, if AFP is ≥ 1.5 x ULN at baseline.
Objective responseduring trial treatment and follow-up (max. 3 years)
Disease stabilization (DS)under trial treatment
Adverse events at baseline and during trial treatmentAll 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 survivalThe 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 stabilizationDuration 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.

Trial Locations

Locations (15)

Medizinische Universität Wien

🇦🇹

Wien, Austria

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

🇨🇭

Bellinzona, Switzerland

Saint Claraspital AG

🇨🇭

Basel, Switzerland

Szent Laszlo Korhaz

🇭🇺

Budapest, Hungary

Clinical Cancer Research Center at University Hospital Basel

🇨🇭

Basel, Switzerland

Inselspital Bern

🇨🇭

Bern, Switzerland

Kantonsspital Bruderholz

🇨🇭

Bruderholz, Switzerland

Centre Hospitalier Universitaire Vaudois

🇨🇭

Lausanne, Switzerland

Hopital Cantonal Universitaire de Geneve

🇨🇭

Geneva, Switzerland

City Hospital Triemli

🇨🇭

Zurich, Switzerland

UniversitaetsSpital Zuerich

🇨🇭

Zurich, Switzerland

Kantonsspital Liestal

🇨🇭

Liestal, Switzerland

Kantonsspital - St. Gallen

🇨🇭

St. Gallen, Switzerland

CHCVS - Hôpital de Sion

🇨🇭

Sion, Switzerland

Regionalspital

🇨🇭

Thun, Switzerland

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