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Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma. (EVOLVE-1)

Primary Purpose

Carcinoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Everolimus
Everolimus Placebo
Best Supportive Care (BSC)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma focused on measuring Hepatocellular carcinoma, randomized trial, medical treatment, RAD001, placebo, Advanced Hepatocellular Carcinoma (HCC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Advanced liver cancer

  • Prior systemic treatment with sorafenib for advanced HCC and for whom their disease progressed during or after sorafenib treatment, or were intolerant to sorafenib treatment. Specifically, this can be defined as:

    • Documented radiological confirmation (radiology scans or report) of disease progression during or after sorafenib treatment
    • Intolerance to sorafenib (at any dose and/or duration) is defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation.

NOTE:

  • Sorafenib must be the last antineoplastic treatment before randomization
  • Prior local and/or hormonal therapy (e.g., tamoxifen) before sorafenib is allowed

  • One systemic chemotherapy regimen for advanced HCC is allowed before sorafenib treatment

    • ECOG performance status of ≤ 2
    • Child-Pugh A

Exclusion Criteria:

  • Active bleeding during the last 28 days
  • Prior therapy with mTOR inhibitors
  • Prior liver or other organ transplantation which mandates systemic immunosuppression

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Highlands Oncology Group Dept of Highlands Oncology Grp
  • Compassionate Cancer Care Medical Group CCCMG
  • University of California San Diego - Moores Cancer Center SC - 3
  • California Pacific Medical Center California Pacific Med
  • Rocky Mountain Cancer Centers RMCC - Denver-Midtown (4)
  • Queen's Medical Center Queens Cancer Center
  • The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Dept. of SKCC @ JHU
  • Massachusetts General Hospital Dept. of Mass General Hospital
  • Midwest Cancer Care Physicians Research Medical Center
  • VA Sierra Nevada Health Care System Dept. of VA Sierra Nevada HCS
  • University of Rochester Medical Center Rochester
  • Northwest Cancer Specialists Rose Quarter Cancer Center
  • St. Luke's Hospital and Health Network St. Luke's Cancer Network (2)
  • Texas Cancer Center - Abilene
  • Methodist Charlton Cancer Center Methodist
  • University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(3)
  • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
  • Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care
  • University of Washington Cancer Care SC
  • Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Everolimus + Best Supportice Care (BSC)

Placebo + Best Supportive Care

Arm Description

Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice.

Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.

Outcomes

Primary Outcome Measures

Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.

Secondary Outcome Measures

Time to Tumor Progression (TTP)
TTP was defined as the time from the date of randomization to the date of the first documented radiologic confirmation of disease progression. Since the study did not meet the primary objective, TTP was not formally tested.
Percentage of Participants With Disease Control Rate (DCR)
DCR is defined as the proportion of participants with a best objective response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST. The BOR was the best response recorded from the start of the treatment until disease progression. CR is disappearance of all target lesions; PR is at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is at least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
Time to Definitive Deterioration of ECOG Performance Score (PS) Score
Change in Eastern Cooperative Oncology Group (ECOG) were assessed by time to definitive performance status deterioration by at least one category on the ECOG scale. Deterioration was considered definitive if no improvement in the ECOG PS was observed at a subsequent measurement. ECOG PS: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5=Dead
Time to Definitive Deterioration of EORTC QLQ-C30 Scores
The primary quality of life endpoint was the time to definitive 5% deterioration from baseline in the global health status/quality of life scale of the EORTC QLQ-C30 questionnaire. Definitive deterioration by at least 5% is defined as a decrease in score by at least 5% compared to baseline, with no later observed increase above this threshold. The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the healthrelated quality of life (QoL) of cancer patients participating in international clinical trials. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Pharmacokinetics Assessments - Cmin
Cmin is the pre-dose blood concentration at steady-state (ng/mL). Pre-dose (Cmin) blood samples were collected from all patients in both arms at Visit 3. Steady-state for the Cmin sample was defined as continuous administration of the same dose in the last 4 days prior to the collection of the Cmin sample. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid pre-dose (Cmin) everolimus samples were included in the analysis.
Pharmacokinetics Assessments - Cmax
Cmax is the maximum (peak) blood drug concentration after dose administration (ng/mL) calculated as the maximum of C1h and C2h. C1h was 1 hour post-dose blood concentration (ng/mL) and C2h was 2 hour post-dose blood concentration (ng/mL). C1h and C2h post-dose samples were collected from all patients in both arms at Visit 3. Steady-state for the C1h and C2h samples was defined as continuous administration of the same dose in the previous 4 days and the day on which the C1h and C2h samples were collected. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid C1h and C2h everolimus samples were included in the analysis.

Full Information

First Posted
December 17, 2009
Last Updated
August 16, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01035229
Brief Title
Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.
Acronym
EVOLVE-1
Official Title
A Randomized Phase III, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Everolimus (RAD001) in Adult Patients With Advanced Hepatocellular Carcinoma After Failure of Sorafenib Treatment - The EVOLVE-1 Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to compare treatment with RAD001 plus best supportive care (BSC) to placebo plus BSC in patients with advanced HCC whose disease progressed while on or after sorafenib treatment or who are intolerant to sorafenib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma
Keywords
Hepatocellular carcinoma, randomized trial, medical treatment, RAD001, placebo, Advanced Hepatocellular Carcinoma (HCC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
546 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus + Best Supportice Care (BSC)
Arm Type
Experimental
Arm Description
Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice.
Arm Title
Placebo + Best Supportive Care
Arm Type
Placebo Comparator
Arm Description
Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Everolimus (labeled as RAD001) was formulated as tablets of 2.5 mg strength and blisterpacked in units of 10 tablets.
Intervention Type
Drug
Intervention Name(s)
Everolimus Placebo
Intervention Description
Everolimus Placebo matched to the everolimus 2.5 mg tablet strength was blister-packed in units of 10 tablets. Matching placebo tablets were formulated to be indistinguishable from the everolimus tablets. Everolimus placebo was taken as a daily oral dose of 7.5 mg and was defined as the control drug.
Intervention Type
Other
Intervention Name(s)
Best Supportive Care (BSC)
Intervention Description
BSC was defined as drug or non-drug therapies, nutritional support, physical therapy or anything that the Investigator believed to be in the patient's best interest, but excluding other antineoplastic treatments. BSC administered to the patient throughout the study was to be reported on the Concomitant Medication/Significant Non-Drug Therapy electronic case report from (eCRF). Permitted BSC treatments during the study included, but were not limited to, the following: Pain medication to allow the patient to be as comfortable as possible, Bisphosphonates for bone metastases, Localized radiotherapy, for the treatment of pre-existing, painful bone metastases, Nutritional support or appetite stimulants (i.e. megestrol) as recommended by the Investigator, Oxygen therapy and blood products or transfusions
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.
Time Frame
When 454 OS events were observed
Secondary Outcome Measure Information:
Title
Time to Tumor Progression (TTP)
Description
TTP was defined as the time from the date of randomization to the date of the first documented radiologic confirmation of disease progression. Since the study did not meet the primary objective, TTP was not formally tested.
Time Frame
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient
Title
Percentage of Participants With Disease Control Rate (DCR)
Description
DCR is defined as the proportion of participants with a best objective response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST. The BOR was the best response recorded from the start of the treatment until disease progression. CR is disappearance of all target lesions; PR is at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is at least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
Time Frame
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient
Title
Time to Definitive Deterioration of ECOG Performance Score (PS) Score
Description
Change in Eastern Cooperative Oncology Group (ECOG) were assessed by time to definitive performance status deterioration by at least one category on the ECOG scale. Deterioration was considered definitive if no improvement in the ECOG PS was observed at a subsequent measurement. ECOG PS: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5=Dead
Time Frame
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.
Title
Time to Definitive Deterioration of EORTC QLQ-C30 Scores
Description
The primary quality of life endpoint was the time to definitive 5% deterioration from baseline in the global health status/quality of life scale of the EORTC QLQ-C30 questionnaire. Definitive deterioration by at least 5% is defined as a decrease in score by at least 5% compared to baseline, with no later observed increase above this threshold. The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the healthrelated quality of life (QoL) of cancer patients participating in international clinical trials. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Time Frame
Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.
Title
Pharmacokinetics Assessments - Cmin
Description
Cmin is the pre-dose blood concentration at steady-state (ng/mL). Pre-dose (Cmin) blood samples were collected from all patients in both arms at Visit 3. Steady-state for the Cmin sample was defined as continuous administration of the same dose in the last 4 days prior to the collection of the Cmin sample. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid pre-dose (Cmin) everolimus samples were included in the analysis.
Time Frame
Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.
Title
Pharmacokinetics Assessments - Cmax
Description
Cmax is the maximum (peak) blood drug concentration after dose administration (ng/mL) calculated as the maximum of C1h and C2h. C1h was 1 hour post-dose blood concentration (ng/mL) and C2h was 2 hour post-dose blood concentration (ng/mL). C1h and C2h post-dose samples were collected from all patients in both arms at Visit 3. Steady-state for the C1h and C2h samples was defined as continuous administration of the same dose in the previous 4 days and the day on which the C1h and C2h samples were collected. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid C1h and C2h everolimus samples were included in the analysis.
Time Frame
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Advanced liver cancer Prior systemic treatment with sorafenib for advanced HCC and for whom their disease progressed during or after sorafenib treatment, or were intolerant to sorafenib treatment. Specifically, this can be defined as: Documented radiological confirmation (radiology scans or report) of disease progression during or after sorafenib treatment Intolerance to sorafenib (at any dose and/or duration) is defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation. NOTE: Sorafenib must be the last antineoplastic treatment before randomization Prior local and/or hormonal therapy (e.g., tamoxifen) before sorafenib is allowed One systemic chemotherapy regimen for advanced HCC is allowed before sorafenib treatment ECOG performance status of ≤ 2 Child-Pugh A Exclusion Criteria: Active bleeding during the last 28 days Prior therapy with mTOR inhibitors Prior liver or other organ transplantation which mandates systemic immunosuppression Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Highlands Oncology Group Dept of Highlands Oncology Grp
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Compassionate Cancer Care Medical Group CCCMG
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
University of California San Diego - Moores Cancer Center SC - 3
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
California Pacific Medical Center California Pacific Med
City
San Francisco
State/Province
California
ZIP/Postal Code
94120-7999
Country
United States
Facility Name
Rocky Mountain Cancer Centers RMCC - Denver-Midtown (4)
City
Greenwood Village
State/Province
Colorado
Country
United States
Facility Name
Queen's Medical Center Queens Cancer Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Dept. of SKCC @ JHU
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-0013
Country
United States
Facility Name
Massachusetts General Hospital Dept. of Mass General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Midwest Cancer Care Physicians Research Medical Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
VA Sierra Nevada Health Care System Dept. of VA Sierra Nevada HCS
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
University of Rochester Medical Center Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Northwest Cancer Specialists Rose Quarter Cancer Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
St. Luke's Hospital and Health Network St. Luke's Cancer Network (2)
City
Bethlehem
State/Province
Pennsylvania
Country
United States
Facility Name
Texas Cancer Center - Abilene
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
Methodist Charlton Cancer Center Methodist
City
Dallas
State/Province
Texas
ZIP/Postal Code
75237
Country
United States
Facility Name
University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(3)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8527
Country
United States
Facility Name
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24018
Country
United States
Facility Name
University of Washington Cancer Care SC
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
Facility Name
Novartis Investigative Site
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Novartis Investigative Site
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Novartis Investigative Site
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Novartis Investigative Site
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Novartis Investigative Site
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Novartis Investigative Site
City
Innsbruck
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 1P1
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
Facility Name
Novartis Investigative Site
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100039
Country
China
Facility Name
Novartis Investigative Site
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Facility Name
Novartis Investigative Site
City
Amiens cedex 1
ZIP/Postal Code
80054
Country
France
Facility Name
Novartis Investigative Site
City
Avignon Cedex
ZIP/Postal Code
84082
Country
France
Facility Name
Novartis Investigative Site
City
Bordeaux Cedex
ZIP/Postal Code
33075
Country
France
Facility Name
Novartis Investigative Site
City
Caen Cedex9
ZIP/Postal Code
14033
Country
France
Facility Name
Novartis Investigative Site
City
Chambray-lès-Tours
ZIP/Postal Code
37170
Country
France
Facility Name
Novartis Investigative Site
City
Clermont Ferrand cedex 1
ZIP/Postal Code
63003
Country
France
Facility Name
Novartis Investigative Site
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Novartis Investigative Site
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Novartis Investigative Site
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Lyon Cedex 04
ZIP/Postal Code
69317
Country
France
Facility Name
Novartis Investigative Site
City
Marseille Cédex 5
ZIP/Postal Code
13385
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Novartis Investigative Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Novartis Investigative Site
City
Nice Cedex 3
ZIP/Postal Code
06202
Country
France
Facility Name
Novartis Investigative Site
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Novartis Investigative Site
City
Rouen Cedex
ZIP/Postal Code
76031
Country
France
Facility Name
Novartis Investigative Site
City
St Priest en Jarez Cedex
ZIP/Postal Code
42277
Country
France
Facility Name
Novartis Investigative Site
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Novartis Investigative Site
City
Mannheim
State/Province
Baden-Württemberg
ZIP/Postal Code
68305
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Esslingen
ZIP/Postal Code
73730
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Goettingen
ZIP/Postal Code
D-37075
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Novartis Investigative Site
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
State/Province
GR
ZIP/Postal Code
124 62
Country
Greece
Facility Name
Novartis Investigative Site
City
Larissa
State/Province
GR
ZIP/Postal Code
411 10
Country
Greece
Facility Name
Novartis Investigative Site
City
Thessaloniki
ZIP/Postal Code
57001
Country
Greece
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
H-1122
Country
Hungary
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szeged
ZIP/Postal Code
H-6720
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szombathely
ZIP/Postal Code
9700
Country
Hungary
Facility Name
Novartis Investigative Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
5266202
Country
Israel
Facility Name
Novartis Investigative Site
City
Benevento
State/Province
BN
ZIP/Postal Code
82100
Country
Italy
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Foggia
State/Province
FG
ZIP/Postal Code
71100
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
Facility Name
Novartis Investigative Site
City
Palermo
State/Province
PA
ZIP/Postal Code
90127
Country
Italy
Facility Name
Novartis Investigative Site
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Novartis Investigative Site
City
Aviano
State/Province
PN
ZIP/Postal Code
33081
Country
Italy
Facility Name
Novartis Investigative Site
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00128
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Facility Name
Novartis Investigative Site
City
Frattamaggiore
ZIP/Postal Code
80020
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Novartis Investigative Site
City
Chiba-city
State/Province
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Novartis Investigative Site
City
Matsuyama
State/Province
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Novartis Investigative Site
City
Iizuka-city
State/Province
Fukuoka
ZIP/Postal Code
820-8505
Country
Japan
Facility Name
Novartis Investigative Site
City
Gifu-shi
State/Province
Gifu
ZIP/Postal Code
500-8513
Country
Japan
Facility Name
Novartis Investigative Site
City
Ogaki-city
State/Province
Gifu
ZIP/Postal Code
503-8502
Country
Japan
Facility Name
Novartis Investigative Site
City
Kanazawa-city
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama-city
State/Province
Kanagawa
ZIP/Postal Code
232-0024
Country
Japan
Facility Name
Novartis Investigative Site
City
Kumamoto City
State/Province
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai-city
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Novartis Investigative Site
City
OsakaSayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Mitaka-city
State/Province
Tokyo
ZIP/Postal Code
181-8611
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinagawa-ku
State/Province
Tokyo
ZIP/Postal Code
141-8625
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka
ZIP/Postal Code
810-8563
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
537-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Cordoba
State/Province
Andalucia
ZIP/Postal Code
14004
Country
Spain
Facility Name
Novartis Investigative Site
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
State/Province
Taiwan, ROC
ZIP/Postal Code
112
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Lin-Kou
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Liouying Township
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Niaosong Township
ZIP/Postal Code
83301
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Tainan
ZIP/Postal Code
70403
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
27130844
Citation
Zhu AX, Chen D, He W, Kanai M, Voi M, Chen LT, Daniele B, Furuse J, Kang YK, Poon RT, Vogel A, Chiang DY. Integrative biomarker analyses indicate etiological variations in hepatocellular carcinoma. J Hepatol. 2016 Aug;65(2):296-304. doi: 10.1016/j.jhep.2016.04.015. Epub 2016 Apr 27.
Results Reference
derived
PubMed Identifier
25058218
Citation
Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, Dorval E, Peck-Radosavljevic M, Santoro A, Daniele B, Furuse J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA. 2014 Jul 2;312(1):57-67. doi: 10.1001/jama.2014.7189.
Results Reference
derived
Links:
URL
https://www.novartisclinicaltrials.com/TrialConnectWeb/home.nov
Description
Related Info

Learn more about this trial

Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.

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