The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01035229




Registration number
NCT01035229
Ethics application status
Date submitted
17/12/2009
Date registered
18/12/2009
Date last updated
22/09/2016

Titles & IDs
Public 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.
Scientific 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
Secondary ID [1] 0 0
2009-010196-25
Secondary ID [2] 0 0
CRAD001O2301
Universal Trial Number (UTN)
Trial acronym
EVOLVE-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Everolimus
Treatment: Drugs - Everolimus Placebo
Other interventions - Best Supportive Care (BSC)

Experimental: Everolimus + Best Supportice Care (BSC) - 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 comparator: Placebo + Best Supportive Care - 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.


Treatment: Drugs: Everolimus
Everolimus (labeled as RAD001) was formulated as tablets of 2.5 mg strength and blisterpacked in units of 10 tablets.

Treatment: Drugs: Everolimus Placebo
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.

Other interventions: Best Supportive Care (BSC)
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

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
When 454 OS events were observed
Secondary outcome [1] 0 0
Time to Tumor Progression (TTP)
Timepoint [1] 0 0
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient
Secondary outcome [2] 0 0
Percentage of Participants With Disease Control Rate (DCR)
Timepoint [2] 0 0
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient
Secondary outcome [3] 0 0
Time to Definitive Deterioration of ECOG Performance Score (PS) Score
Timepoint [3] 0 0
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.
Secondary outcome [4] 0 0
Time to Definitive Deterioration of EORTC QLQ-C30 Scores
Timepoint [4] 0 0
Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.
Secondary outcome [5] 0 0
Pharmacokinetics Assessments - Cmin
Timepoint [5] 0 0
Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.
Secondary outcome [6] 0 0
Pharmacokinetics Assessments - Cmax
Timepoint [6] 0 0
Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [3] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [4] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [5] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Hawaii
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Austria
State/province [16] 0 0
Innsbruck
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Bruxelles
Country [19] 0 0
Belgium
State/province [19] 0 0
Edegem
Country [20] 0 0
Belgium
State/province [20] 0 0
Leuven
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
China
State/province [23] 0 0
Jiangsu
Country [24] 0 0
China
State/province [24] 0 0
Shanxi
Country [25] 0 0
China
State/province [25] 0 0
Sichuan
Country [26] 0 0
China
State/province [26] 0 0
Zhejiang
Country [27] 0 0
China
State/province [27] 0 0
Beijing
Country [28] 0 0
China
State/province [28] 0 0
Guangzhou
Country [29] 0 0
France
State/province [29] 0 0
Amiens cedex 1
Country [30] 0 0
France
State/province [30] 0 0
Avignon Cedex
Country [31] 0 0
France
State/province [31] 0 0
Bordeaux Cedex
Country [32] 0 0
France
State/province [32] 0 0
Caen Cedex9
Country [33] 0 0
France
State/province [33] 0 0
Chambray-lès-Tours
Country [34] 0 0
France
State/province [34] 0 0
Clermont Ferrand cedex 1
Country [35] 0 0
France
State/province [35] 0 0
Clichy
Country [36] 0 0
France
State/province [36] 0 0
Dijon
Country [37] 0 0
France
State/province [37] 0 0
Lille Cedex
Country [38] 0 0
France
State/province [38] 0 0
Lyon Cedex 04
Country [39] 0 0
France
State/province [39] 0 0
Marseille Cédex 5
Country [40] 0 0
France
State/province [40] 0 0
Montpellier Cedex 5
Country [41] 0 0
France
State/province [41] 0 0
Nantes Cedex 1
Country [42] 0 0
France
State/province [42] 0 0
Nice Cedex 3
Country [43] 0 0
France
State/province [43] 0 0
Reims
Country [44] 0 0
France
State/province [44] 0 0
Rouen Cedex
Country [45] 0 0
France
State/province [45] 0 0
St Priest en Jarez Cedex
Country [46] 0 0
France
State/province [46] 0 0
Strasbourg
Country [47] 0 0
Germany
State/province [47] 0 0
Baden-Württemberg
Country [48] 0 0
Germany
State/province [48] 0 0
Berlin
Country [49] 0 0
Germany
State/province [49] 0 0
Essen
Country [50] 0 0
Germany
State/province [50] 0 0
Esslingen
Country [51] 0 0
Germany
State/province [51] 0 0
Frankfurt
Country [52] 0 0
Germany
State/province [52] 0 0
Goettingen
Country [53] 0 0
Germany
State/province [53] 0 0
Hamburg
Country [54] 0 0
Germany
State/province [54] 0 0
Hannover
Country [55] 0 0
Germany
State/province [55] 0 0
Leipzig
Country [56] 0 0
Germany
State/province [56] 0 0
Muenchen
Country [57] 0 0
Germany
State/province [57] 0 0
Würzburg
Country [58] 0 0
Greece
State/province [58] 0 0
GR
Country [59] 0 0
Greece
State/province [59] 0 0
Thessaloniki
Country [60] 0 0
Hong Kong
State/province [60] 0 0
Hong Kong
Country [61] 0 0
Hungary
State/province [61] 0 0
Budapest
Country [62] 0 0
Hungary
State/province [62] 0 0
Debrecen
Country [63] 0 0
Hungary
State/province [63] 0 0
Szeged
Country [64] 0 0
Hungary
State/province [64] 0 0
Szombathely
Country [65] 0 0
Israel
State/province [65] 0 0
Petach Tikva
Country [66] 0 0
Israel
State/province [66] 0 0
Ramat Gan
Country [67] 0 0
Italy
State/province [67] 0 0
BN
Country [68] 0 0
Italy
State/province [68] 0 0
BO
Country [69] 0 0
Italy
State/province [69] 0 0
FG
Country [70] 0 0
Italy
State/province [70] 0 0
MI
Country [71] 0 0
Italy
State/province [71] 0 0
MO
Country [72] 0 0
Italy
State/province [72] 0 0
PA
Country [73] 0 0
Italy
State/province [73] 0 0
PD
Country [74] 0 0
Italy
State/province [74] 0 0
PN
Country [75] 0 0
Italy
State/province [75] 0 0
PV
Country [76] 0 0
Italy
State/province [76] 0 0
RM
Country [77] 0 0
Italy
State/province [77] 0 0
Frattamaggiore
Country [78] 0 0
Italy
State/province [78] 0 0
Napoli
Country [79] 0 0
Japan
State/province [79] 0 0
Aichi
Country [80] 0 0
Japan
State/province [80] 0 0
Chiba
Country [81] 0 0
Japan
State/province [81] 0 0
Ehime
Country [82] 0 0
Japan
State/province [82] 0 0
Fukuoka
Country [83] 0 0
Japan
State/province [83] 0 0
Gifu
Country [84] 0 0
Japan
State/province [84] 0 0
Ishikawa
Country [85] 0 0
Japan
State/province [85] 0 0
Kanagawa
Country [86] 0 0
Japan
State/province [86] 0 0
Kumamoto
Country [87] 0 0
Japan
State/province [87] 0 0
Miyagi
Country [88] 0 0
Japan
State/province [88] 0 0
Osaka
Country [89] 0 0
Japan
State/province [89] 0 0
Tokyo
Country [90] 0 0
Korea, Republic of
State/province [90] 0 0
Korea
Country [91] 0 0
Spain
State/province [91] 0 0
Andalucia
Country [92] 0 0
Spain
State/province [92] 0 0
Barcelona
Country [93] 0 0
Spain
State/province [93] 0 0
Catalunya
Country [94] 0 0
Spain
State/province [94] 0 0
Navarra
Country [95] 0 0
Spain
State/province [95] 0 0
Madrid
Country [96] 0 0
Taiwan
State/province [96] 0 0
Taiwan, ROC
Country [97] 0 0
Taiwan
State/province [97] 0 0
Lin-Kou
Country [98] 0 0
Taiwan
State/province [98] 0 0
Liouying Township
Country [99] 0 0
Taiwan
State/province [99] 0 0
Niaosong Township
Country [100] 0 0
Taiwan
State/province [100] 0 0
Taichung
Country [101] 0 0
Taiwan
State/province [101] 0 0
Tainan
Country [102] 0 0
Taiwan
State/province [102] 0 0
Taipei
Country [103] 0 0
Thailand
State/province [103] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.