Clinical trial NCT00828594: Global Study Looking at the Combination of RAD001 and Sorafenib to Treat Patients With Advanced Hepatocellular Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
dose-finding study
randomized trial
medical treatment
RAD001
sorafenib
Advanced hepatocellular cancer (HCC)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-01-26
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose of combination RAD001+sorafenib
timeFrame: Until maximum tolerated dose is determined
measure: Time to disease progression assessed when 60 events have been observed
timeFrame: Until number of events are reached
Secondary outcomes:
measure: Safety and tolerability of the combination of RAD001 plus sorafenib as measured by the rate and severity of adverse events
timeFrame: Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity
measure: Tumor response
timeFrame: Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity
measure: Biomarkers- effect of treatment on soluble markers of angiogenesis and apoptosis
timeFrame: Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity
measure: Overall tumor response (phase 2)
timeFrame: Estimate of 1 year for each patient - Until number of events reached and final analysis
measure: Progression Free Survivor, Overall Survivor (phase 2)
timeFrame: Estimate of 1 year for each patient - Until number of events reached and final analysis
measure: Safety and tolerability - of the combination of RAD001 plus sorafenib as measured by the rate and severity of adverse events (phase 2)
timeFrame: Estimate of 1 year for each patient - Until number of events reached and final analysis
measure: Pharmokinetics of RAD001 at pre-dose and 1 hour and 2 hours post-dose (phase 2)
timeFrame: Estimate of 1 year for each patient - Until number of events reached and final analysis
measure: Biomarkers effect of treatment on soluble markers of angiogenesis and apoptosis (phase 2)
timeFrame: Estimate of 1 year for each patient - Until number of events reached and final analysis
measure: Pharmokinetics of RAD001 at pre-dose and 1 hour and 2 hours post-dose
timeFrame: Estimate of 1 year for each patient - Until all patients have disease progression or leave study due to intolerable toxicity
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine
state: California
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Invstigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: