Clinical trial NCT03847428: Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Early stage HCC
Durvalumab
Bevacizumab
Liver Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-02-20
Enrollment: 908
Sex: ALL
Minimum age (years): 18
Maximum age (years): 150
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recurrence-free survival (RFS) for Arm A vs Arm C
timeFrame: Up to 49 months after first patient randomized
Secondary outcomes:
measure: Recurrence-free survival (RFS) Arm B vs Arm C
timeFrame: Up to 49 months after first patient randomized
measure: Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C
timeFrame: No timeframe
measure: Recurrence-free survival at 24 months (RFS24) and 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C
timeFrame: At 24 and at 36 months
measure: Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C
timeFrame: Up to 49 months after first patient randomized
measure: Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C
timeFrame: Up to 49 months after first patient randomized
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Costa Mesa
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Long Beach
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state: California
city: Orange
country: United States
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state: California
city: Sacramento
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state: California
city: Washington
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facility: Research Site
state: District of Columbia
city: Miami
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state: Florida
city: Tampa
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state: Michigan
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state: Ontario
city: Kingston
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city: Ottawa
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city: Toronto
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city: Toronto
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state: Ontario
city: Quebec
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Bengbu
country: China
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city: Changchun
country: China
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city: Changsha
country: China
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country: China
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country: China
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country: China
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city: Guangzhou
country: China
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country: China
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city: Hangzhou
country: China
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city: Hangzhou
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: Hohhot
country: China
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city: Nanjing
country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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city: Urumqi
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
facility: Research Site
city: Alexandria
country: Egypt
facility: Research Site
city: Assiut
country: Egypt
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city: Cairo
country: Egypt
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city: Cairo
country: Egypt
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city: Cairo
country: Egypt
facility: Research Site
city: Dakahlia
country: Egypt
facility: Research Site
city: New Cairo
country: Egypt
facility: Research Site
city: Shebeen El Kom
country: Egypt
facility: Research Site
city: Amiens Cedex 1
country: France
facility: Research Site
city: ANGERS Cedex 9
country: France
facility: Research Site
city: Besançon
country: France
facility: Research Site
city: Clichy
country: France
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city: Dijon Cedex
country: France
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city: Nantes
country: France
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city: Nice
country: France
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city: PARIS Cedex 12
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
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city: TOURS Cedex 9
country: France
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city: Berlin
country: Germany
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city: Bonn
country: Germany
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city: Chemnitz
country: Germany
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city: Freiburg
country: Germany
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city: Heidelberg
country: Germany
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city: Köln
country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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city: Hong Kong
country: Hong Kong
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country: India
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country: India
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country: India
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city: Bologna
country: Italy
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city: Milano
country: Italy
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city: Milano
country: Italy
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city: Napoli
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city: Roma
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city: Tricase, Lecce
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city: Verona
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
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city: Fukuoka-shi
country: Japan
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city: Gifu-shi
country: Japan
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city: Hiroshima-shi
country: Japan
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country: Japan
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city: Kumamoto-shi
country: Japan
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city: Kurume-shi
country: Japan
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city: Kyoto-shi
country: Japan
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city: Kyoto-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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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: Sapporo-shi
country: Japan
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city: Sendai-shi
country: Japan
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city: Shinagawa-ku
country: Japan
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city: Shinjuku-ku
country: Japan
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city: Shinjuku-ku
country: Japan
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city: Shiwa-gun
country: Japan
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city: Takasaki-shi
country: Japan
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city: Tsu-shi
country: Japan
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city: Wakayama-shi
country: Japan
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city: Yokohama-shi
country: Japan
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city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
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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
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country: Korea, Republic of
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city: Lima
country: Peru
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country: Peru
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country: Peru
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country: Peru
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city: Manila
country: Philippines
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city: Muntinlupa City
country: Philippines
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city: Pasig City
country: Philippines
facility: Research Site
city: Bydgoszcz
country: Poland
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city: Gdańsk
country: Poland
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city: Poznań
country: Poland
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city: Warszawa
country: Poland
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city: Ponce
country: Puerto Rico
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city: Barnaul
country: Russian Federation
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city: Ekaterinburg
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Obninsk
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: Singapore
country: Singapore
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city: Singapore
country: Singapore
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city: Singapore
country: Singapore
facility: Research Site
city: Changhua
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
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city: Taoyuan City
country: Taiwan
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city: Yunlin
country: Taiwan
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city: Bangkok
country: Thailand
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city: Bangkok
country: Thailand
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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: Pathumthani
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
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
city: Hochiminh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Liver Cancer Institute Zhongshan Hospital, Fudan University
name: Jia Fan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Solid Tumor Medical Oncology Princess Margaret Cancer Centre
name: Jennifer Knox, MD
role: PRINCIPAL_INVESTIGATOR
References: