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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT00828594

Collaborator

(none)

130

Enrollment

Locations

Arm

Duration (Months)

16.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: RAD001 Drug: RAD001, sorafenib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

130 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1: RAD001 plus sorafenib	Drug: RAD001 Drug: RAD001, sorafenib

Arm

Intervention/Treatment

Experimental: Phase 1: RAD001 plus sorafenib

Drug: RAD001

Drug: RAD001, sorafenib

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010
2	UCLA Department of Medicine	Los Angeles	California	United States	90005
3	Duke University	Durham	North Carolina	United States	27710
4	Novartis Investigative Site	Seoul		Korea, Republic of
5	Novartis Investigative Site	Amsterdam		Netherlands
6	Novartis Investigative Site	Barcelona		Spain
7	Novartis Invstigative Site	Madrid		Spain
8	Novartis Investigative Site	Tainan		Taiwan