Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment

Hepatocellular Carcinoma Clinical Trial

— EMERALD-2  

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi Center Study of Durvalumab Monotherapy or in Combination With Bevacizumab as Adjuvant Therapy in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection or Ablation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03847428
• Other study ID #: D910DC00001
• Secondary ID: 2018-004105-85
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 29, 2019
• Est. completion date: May 31, 2027

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab alone in patients with hepatocellular carcinoma who are at high risk of recurrence.

Description:

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab monotherapy or placebo as adjuvant therapy. This study will be conducted in patients with HCC who are at high risk of recurrence after curative hepatic resection or ablation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 908
• Est. completion date: May 31, 2027
• Est. primary completion date: May 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 150 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically (or radiologically for patients undergoing curative ablation), newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation)
• Imaging to confirm disease-free status within 28 days prior to randomization
• ECOG 0-1 at enrolment
• Child-Pugh score of 5 or 6
• Adequate organ and marrow function.

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC
• Evidence of metastasis, macrovascular invasion or co-existing malignant disease on baseline imaging
• History of hepatic encephalopathy within 12 months prior to randomization
• Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging
• Patients with Vp1 to Vp4 portal vein thrombosis on baseline imaging are excluded
• Active co-infection with HBV and HDV.
• Receipt of prior systemic anticancer therapy for HCC
• Those on a waiting list for liver transplantation

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Recurrence

Intervention

Drug:
• Durvalumab
Durvalumab IV (intravenous)
• Bevacizumab
Bevacizumab IV (intravenous)

Other:
• Placebo
Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking

Locations

Country	Name	City	State
Australia	Research Site	Kogarah
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	Westmead
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	St. Pölten
Brazil	Research Site	Florianópolis
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santa Maria
Brazil	Research Site	Santo Andre
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Vitória
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Hohhot
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Zhengzhou
Egypt	Research Site	Alexandria
Egypt	Research Site	Assiut
Egypt	Research Site	Cairo
Egypt	Research Site	Cairo
Egypt	Research Site	Cairo
Egypt	Research Site	Dakahlia
Egypt	Research Site	New Cairo
Egypt	Research Site	Shebeen El Kom
France	Research Site	Amiens Cedex 1
France	Research Site	ANGERS Cedex 9
France	Research Site	Besançon
France	Research Site	Clichy
France	Research Site	Dijon Cedex
France	Research Site	Nantes
France	Research Site	Nice
France	Research Site	PARIS Cedex 12
France	Research Site	Pessac
France	Research Site	Toulouse Cedex 9
France	Research Site	TOURS Cedex 9
Germany	Research Site	Berlin
Germany	Research Site	Bonn
Germany	Research Site	Chemnitz
Germany	Research Site	Freiburg
Germany	Research Site	Heidelberg
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	München
Germany	Research Site	Tuebingen
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	HongKong
Hong Kong	Research Site	Kwai Chung
Hong Kong	Research Site	Shatin
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Hyderabad
India	Research Site	Kolkata
India	Research Site	Mumbai
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	New Delhi
Italy	Research Site	Bologna
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Roma
Italy	Research Site	Tricase, Lecce
Italy	Research Site	Verona
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Gifu-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Mitaka-shi
Japan	Research Site	Musashino-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shiwa-gun
Japan	Research Site	Takasaki-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	San Isidro
Philippines	Research Site	Manila
Philippines	Research Site	Muntinlupa City
Philippines	Research Site	Pasig City
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Puerto Rico	Research Site	Ponce
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Taiwan	Research Site	Changhua
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan City
Taiwan	Research Site	Yunlin
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Pathumthani
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Malatya
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Birmingham	Alabama
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Costa Mesa	California
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Durham	North Carolina
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Jolla	California
United States	Research Site	Long Beach	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	Mobile	Alabama
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Rochester	Minnesota
United States	Research Site	Sacramento	California
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Stony Brook	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Washington	District of Columbia
United States	Research Site	Westwood	Kansas
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city
Vietnam	Research Site	Hochiminh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Austria,  Brazil,  Canada,  China,  Egypt,  France,  Germany,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  Peru,  Philippines,  Poland,  Puerto Rico,  Russian Federation,  Singapore,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-free survival (RFS) for Arm A vs Arm C	RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first.	Up to 49 months after first patient randomized
Secondary	Recurrence-free survival (RFS) Arm B vs Arm C	RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first.	Up to 49 months after first patient randomized
Secondary	Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C	OS is defined as the time from the date of randomization until death due to any cause	No timeframe
Secondary	Recurrence-free survival at 24 months (RFS24) and 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C	Proportion of RFS at 24 months and at 36 months	At 24 and at 36 months
Secondary	Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C	TTR is defined as the time from the date of randomization until the date of disease recurrence	Up to 49 months after first patient randomized
Secondary	Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C	Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)	Up to 49 months after first patient randomized