Clinical trial NCT03778957: A Global Study to Evaluate Transarterial Chemoembolization (TACE) in Combination With Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma
Official title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Transarterial Chemoembolization (TACE) in Combination With Either Durvalumab Monotherapy or Durvalumab Plus Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
TACE
Durvalumab
Bevacizumab
Liver Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-12-19
Enrollment: 724
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab and bevacizumab therapy in patients with locoregional hepatocellular carcinoma

Detailed description: This is a randomized, double-blind, placebo-controlled, multicenter, global Phase III study to determine the efficacy and safety of transarterial chemoembolization (TACE) treatment in combination with durvalumab monotherapy or TACE given with durvalumab plus bevacizumab therapy compared to TACE therapy alone in patients with locoregional hepatocellular carcinoma not amenable to curative therapy

Eligibility criteria: Key Inclusion Criteria:

* No evidence of extrahepatic disease
* Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE
* Child-Pugh score class A to B7 and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
* Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria
* Adequate organ and marrow function

Key Exclusion Criteria

* Any history of nephrotic or nephritic syndrome
* Clinically significant cardiovascular disease or history of arterioembolic event including a stroke or myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within 6 months prior to randomization
* Any prior or current evidence of coagulopathy or bleeding diathesis or patients who had any kind of surgery in the past 28 days (biopsies are exempt from this exclusion)
* History of abdominal fistula or GI perforation, non healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment
* Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded

Primary outcomes:
measure: Progression Free Survival (PFS) for Arm B vs Arm C
timeFrame: Approximately 5 years
Secondary outcomes:
measure: Progression Free Survival (PFS) for Arm A vs Arm C
timeFrame: Approximately 5 years
measure: Overall Survival (OS)
timeFrame: Approximately 5 years
measure: Health status/quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30)
timeFrame: Approximately 5 years
measure: Disease-related symptoms measured by European Organization for Research and Treatment of Cancer (EORTC) 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18)
timeFrame: Approximately 5 years
Other outcomes:
measure: Safety of Durvalumab and Bevacizumab as evaluated by summary of adverse events by treatment arm and CTCAE grade
timeFrame: Approximately 5 years
measure: Immunogenicity of Durvalumab and Bevacizumab as measured by presence of anti-drug antibodies (ADAs)
timeFrame: Approximately 5 years
measure: Pharmacokinetics (PK) of Durvalumab and Bevacizumab as determined by peak serum concentrations
timeFrame: Approximately 5 years
Locations:
city: Costa Mesa
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
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state: Ohio
city: Portland
country: United States
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state: Oregon
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Sioux Falls
country: United States
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state: South Dakota
city: Memphis
country: United States
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state: Tennessee
city: Dallas
country: United States
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state: Texas
city: Dallas
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Milwaukee
country: United States
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state: Wisconsin
city: Benowa
country: Australia
facility: Research Site
city: Box Hill
country: Australia
facility: Research Site
city: Camperdown
country: Australia
facility: Research Site
city: Clayton
country: Australia
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city: Herston
country: Australia
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city: Liverpool
country: Australia
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city: Melbourne
country: Australia
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Rio de Janeiro
country: Brazil
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city: Santa Maria
country: Brazil
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city: Sao Paulo
country: Brazil
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city: São José do Rio Preto
country: Brazil
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city: Vitória
country: Brazil
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city: Ottawa
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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city: Fuzhou
country: China
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city: Fuzhou
country: China
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city: Guangzhou
country: China
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city: Guangzhou
country: China
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city: Guangzhou
country: China
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city: Hangzhou
country: China
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city: Harbin
country: China
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city: Hefei
country: China
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city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nantong
country: China
facility: Research Site
city: Neijiang
country: China
facility: Research Site
city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: Shenzhen
country: China
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city: Tianjin
country: China
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city: Wuhan
country: China
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city: Wuhan
country: China
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city: Xi'an
country: China
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city: Zhengzhou
country: China
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city: Zhuhai
country: China
facility: Research Site
city: Bobigny
country: France
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city: Clichy
country: France
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city: Grenoble cedex 9
country: France
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city: Montpellier CEDEX 5
country: France
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city: Nice Cedex 3
country: France
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city: Paris Cedex 13
country: France
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city: Pessac
country: France
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city: Toulouse Cedex 9
country: France
facility: Research Site
city: Vandoeuvre Les Nancy
country: France
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Bengaluru
country: India
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city: Hyderabad
country: India
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city: Kolkata
country: India
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city: Kolkata
country: India
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city: Madurai
country: India
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city: Mumbai
country: India
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city: Nashik
country: India
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city: Pune
country: India
facility: Research Site
city: Surat
country: India
facility: Research Site
city: Vijayawada
country: India
facility: Research Site
city: Vishakhapatnam
country: India
facility: Research Site
city: Arezzo
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
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city: Hiroshima-shi
country: Japan
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city: Kurume-shi
country: Japan
facility: Research Site
city: Musashino-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Okayama
country: Japan
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city: Osaka-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Osakasayama-shi
country: Japan
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city: Sapporo-shi
country: Japan
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city: Shiwa-gun
country: Japan
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city: Tsu-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Research Site
city: Alc. Cuauhtémoc
country: Mexico
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city: Culiacan
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
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city: Monterrey
country: Mexico
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city: Monterrey
country: Mexico
facility: Research Site
city: Mérida
country: Mexico
facility: Research Site
city: Tuxtla Gutierrez
country: Mexico
facility: Research Site
city: Barnaul
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Sankt-Peterburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Bukit Merah
country: Singapore
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: San Sebastián(Guipuzcoa)
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Liou Ying Township
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
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city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Phisanulok
country: Thailand
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Clinica Universidad de Navarra
name: Bruno Sangro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pisa / Miami Cancer Institute
name: Riccardo Lencioni, MD FSIR EBIR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1:137-149. doi: 10.1002/hep.31424. Epub 2020 Nov 6. No abstract available.