hepatocellular carcinoma RAD001 sorafenib everolimus Leverkanker RAD001 sorafenib everolimus
Conditions
Interventions
Phase I is an open-label, non-randomized, multi-center, designed as a sequential dose-escalation study combining daily RAD001 plus daily sorafenib, after which phase II will be initiated in sequence
2. Sorafenib 400 mg BID + placebo to RAD001.
Sponsors
Novartis Pharma
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female patients ¡Ý 18 years old with ability to take oral drugs; 2. Diagnosis of advanced HCC according to the AASLD Guidelines (Bruix and Sherman 2005); 3. HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC); 4. No previous systemic therapy for HCC; 5. Measurable disease as per RECIST, that is, at least one lesion that has not been previously treated with local therapy. Previously treated lesions will be considered ¡°non target¡± lesion. Local therapy must be completed at least four weeks prior to baseline scans; 6. Patients with ECOG performance status of 0 or 1; 7. Cirrhotic status of current Child-Pugh class A only (5-6 points) with no encephalopathy. Child-Pugh status should be calculated based on clinical findings and laboratory results during screening period.
Exclusion criteria
Exclusion criteria: 1. Patients currently receiving any anti cancer therapy or who have received any local anti cancer therapy ¡Ü4 weeks prior to study treatment start; 2. Active bleeding during the last 30 days; 3. Known previous/current malignancy ¡Ü 3 years except for cervical carcinoma in situ, basal cell carcinoma, superficial bladder carcinoma; 4. Known central nervous system disease; 5. Known history of HIV seropositivity (HIV testing is not mandatory); 6. Any severe and/or uncontrolled medical conditions; 7. Patients receiving chronic treatment with any systemic immunosuppressive agent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: 1. Dose Limiting Toxicities (DLT) of treatment combination of RAD001 plus sorafenib; 2. Pharmacokinetic measures of systemic exposure, such as AUC, Cmax and trough blood levels. Both Phase I and II: Efficacy evaluation based on the overall response rate according to RECIST. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Clinical efficacy in terms of: A. Objective response rate (ORR); B. Disease control rate (DCR); C. Progression-free survival (PFS), according to RECIST. 2. Safety and tolerability: rate and severity of adverse events. | — |
Contacts
Public ContactH.J. Klümpen
Postbus 22660
Outcome results
None listed