Clinical trial NCT01035229: Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma
Keywords: Hepatocellular carcinoma
randomized trial
medical treatment
RAD001
placebo
Advanced Hepatocellular Carcinoma (HCC)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-12-18
Enrollment: 546
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: When 454 OS events were observed
Secondary outcomes:
measure: Time to Tumor Progression (TTP)
timeFrame: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient
measure: Percentage of Participants With Disease Control Rate (DCR)
timeFrame: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient
measure: Time to Definitive Deterioration of ECOG Performance Score (PS) Score
timeFrame: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.
measure: Time to Definitive Deterioration of EORTC QLQ-C30 Scores
timeFrame: Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.
measure: Pharmacokinetics Assessments - Cmin
timeFrame: Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.
measure: Pharmacokinetics Assessments - Cmax
timeFrame: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group CCCMG
state: California
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center SC - 3
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center California Pacific Med
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC - Denver-Midtown (4)
state: Colorado
city: Honolulu
country: United States
facility: Queen's Medical Center Queens Cancer Center
state: Hawaii
city: Baltimore
country: United States
facility: The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Dept. of SKCC @ JHU
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Dept. of Mass General Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Midwest Cancer Care Physicians Research Medical Center
state: Missouri
city: Reno
country: United States
facility: VA Sierra Nevada Health Care System Dept. of VA Sierra Nevada HCS
state: Nevada
city: Rochester
country: United States
facility: University of Rochester Medical Center Rochester
state: New York
city: Portland
country: United States
facility: Northwest Cancer Specialists Rose Quarter Cancer Center
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network St. Luke's Cancer Network (2)
state: Pennsylvania
city: Abilene
country: United States
facility: Texas Cancer Center - Abilene
state: Texas
city: Dallas
country: United States
facility: Methodist Charlton Cancer Center Methodist
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(3)
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
state: Texas
city: Roanoke
country: United States
facility: Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: University of Washington Cancer Care SC
state: Washington
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Xi'an
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
city: Amiens cedex 1
country: France
facility: Novartis Investigative Site
city: Avignon Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Caen Cedex9
country: France
facility: Novartis Investigative Site
city: Chambray-lès-Tours
country: France
facility: Novartis Investigative Site
city: Clermont Ferrand cedex 1
country: France
facility: Novartis Investigative Site
city: Clichy
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Lyon Cedex 04
country: France
facility: Novartis Investigative Site
city: Marseille Cédex 5
country: France
facility: Novartis Investigative Site
city: Montpellier Cedex 5
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Nice Cedex 3
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Rouen Cedex
country: France
facility: Novartis Investigative Site
city: St Priest en Jarez Cedex
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
state: Baden-Württemberg
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Esslingen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Goettingen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Larissa
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Szombathely
country: Hungary
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Benevento
country: Italy
facility: Novartis Investigative Site
state: BN
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Foggia
country: Italy
facility: Novartis Investigative Site
state: FG
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Frattamaggiore
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Chiba-city
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Matsuyama
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Iizuka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Gifu-shi
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Ogaki-city
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Kanazawa-city
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Sendai-city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: OsakaSayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Mitaka-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan, ROC
city: Lin-Kou
country: Taiwan
facility: Novartis Investigative Site
city: Liouying Township
country: Taiwan
facility: Novartis Investigative Site
city: Niaosong Township
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.
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.