Global Study Looking at the Combination of RAD001 and Sorafenib to Treat Patients With Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Phase 1 Evaluate the safety and tolerability of RAD001 in combination with sorafenib in patients with advance hepatocellular cancer (HCC) and to determine the maximum tolerated dose (MTD) Phase 2 To estimate the treatment effect as a measure of anti-tumor activity in terms of Time to Progression (TTP) of the combination of RAD001 plus sorafenib, at the MTD, as compared to sorafenib alone

Official Title
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A Phase 1 Open Label/ Phase 2 Randomized, Double-blind, Multicenter Study Investigating the Combination of RAD001 and Sorafenib (Nexavar®) in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: RAD001
* Drug: RAD001, sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced liver cancer No previous systemic therapy for liver cancer Measurable disease on CT or MRI ECOG 1 or less Child-Pugh A Exclusion Criteria: Active bleeding during the last 30 days Known history of HIV seropositivity Any severe and/or uncontrolled medical conditions including Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: RAD001 plus sorafenib<br> | Drug: RAD001<br> <br> Drug: RAD001, sorafenib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of combination RAD001+sorafenib |  | Until maximum tolerated dose is determined | 
| Time to disease progression assessed when 60 events have been observed |  | Until number of events are reached | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the combination of RAD001 plus sorafenib as measured by the rate and severity of adverse events |  | Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity | 
| Tumor response |  | Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity | 
| Biomarkers- effect of treatment on soluble markers of angiogenesis and apoptosis |  | Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity | 
| Overall tumor response (phase 2) |  | Estimate of 1 year for each patient - Until number of events reached and final analysis | 
| Progression Free Survivor, Overall Survivor (phase 2) |  | Estimate of 1 year for each patient - Until number of events reached and final analysis | 
| Safety and tolerability - of the combination of RAD001 plus sorafenib as measured by the rate and severity of adverse events (phase 2) |  | Estimate of 1 year for each patient - Until number of events reached and final analysis | 
| Pharmokinetics of RAD001 at pre-dose and 1 hour and 2 hours post-dose (phase 2) |  | Estimate of 1 year for each patient - Until number of events reached and final analysis | 
| Biomarkers effect of treatment on soluble markers of angiogenesis and apoptosis (phase 2) |  | Estimate of 1 year for each patient - Until number of events reached and final analysis | 
| Pharmokinetics of RAD001 at pre-dose and 1 hour and 2 hours post-dose |  | Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, dose-finding study, randomized trial, medical treatment, RAD001, sorafenib, Advanced hepatocellular cancer (HCC)