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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00828594
First received: January 9, 2009
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Hepatocellular Carcinoma
Drug: RAD001
Drug: RAD001, sorafenib
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Maximum tolerated dose of combination RAD001+sorafenib [ Time Frame: Until maximum tolerated dose is determined ] [ Designated as safety issue: Yes ]
  • Time to disease progression assessed when 60 events have been observed [ Time Frame: Until number of events are reached ] [ Designated as safety issue: Yes ]

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

Enrollment: 130
Study Start Date: December 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1: RAD001 plus sorafenib Drug: RAD001 Drug: RAD001, sorafenib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00828594

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
UCLA Department of Medicine
Los Angeles, California, United States, 90005
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Republic of
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands
Spain
Novartis Investigative Site
Barcelona, Spain
Novartis Invstigative Site
Madrid, Spain
Taiwan
Novartis Investigative Site
Tainan, Taiwan
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00828594     History of Changes
Other Study ID Numbers: CRAD001O2101
Study First Received: January 9, 2009
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration
Korea: Food and Drug Administration
Spain: Ethics Committee
Taiwan: Department of Health
Hong Kong: Department of Health
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Novartis:
Hepatocellular carcinoma
dose-finding study
randomized trial
medical treatment
RAD001
sorafenib
Advanced hepatocellular cancer (HCC)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sirolimus
Everolimus
Sorafenib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014