Anlotinib Hydrochloride Capsules Combined With Penpulimab Injection for the Treatment of Hepatocellular Carcinoma at High Risk of Recurrence.

Hepatocellular Carcinoma Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 3 Study of Anlotinib Hydrochloride Capsules Combined With Penpulimab Injection in Patients With High Risk of Relapse After Radical Surgery or Ablation of Hepatocellular Carcinoma (HCC).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05862337
• Other study ID #: ALTN-AK105-III-06
• Status: Recruiting
• Phase: Phase 3
• Start date: May 10, 2023
• Est. completion date: December 2026

Study information

• Verified date: July 2022
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to evaluate the efficacy of anlotinib hydrochloride capsules combined with penpulimab injection (test group) versus placebo (control group) for adjuvant therapy after radical surgery or ablation in HCC patients with high risk of recurrence by assessing recurrence-free survival (RFS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 480
• Est. completion date: December 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 1; Predicted survival =12 weeks.

• Subjects with hepatocellular carcinoma (HCC) confirmed by histopathology or cytology or who meet the diagnostic criteria for Primary Liver Cancer 2022 or the American Association for the Study of Hepatology (AASLD) hepatocellular carcinoma.

• Subjects who received radical excision or ablation (Radio Frequency Ablation (RFA) or Microwave Ablation (MWA) only) within 4 to 12 weeks prior to randomization (multiple modalities or combined or multiple treatments are not acceptable).

• No major vena portae 3 (Vp3) or vena portae 4 (Vp4) in the portal vein or any level of vascular invasion in the hepatic vein or inferior vena cava.

• No extrahepatic metastasis.

• High risk factors for recurrence after radical resection or complete ablation.

• Complete recovery from surgical resection or ablation within 4 weeks before randomization.

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology.

• Evidence of residual, recurrent, or metastatic disease at randomization.

• More than one surgical treatment for hepatocellular carcinoma; Received more than 1 prophylactic Transcatheter Arterial Chemoembolization (TACE) treatment after surgery; or received Hepatic Artery Infusion Chemotherapy (HAIC) therapy after surgery.

• Previous use of antiangiogenic drugs or PD-1, Programmed Cell Death-Ligand 1 (PD-L1) and other related immunotherapy drugs or systemic chemotherapy drugs.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Anlotinib hydrochloride capsules, Penpulimab injection
Anlotinib hydrochloride capsules is a multitargeted receptor tyrosine kinase inhibitor. Penpulimab injection is a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1).
• Anlotinib hydrochloride capsules -matching placebo, Penpulimab injection -matching placebo
placebo control, no active substance.

Locations

Country	Name	City	State
China	Baoji Central Hospital	Baoji	Shanxi
China	Beijing Friendship hospital of Capital Medical University	Beijing	Beijing
China	Beijing YouAn Hospital,Capital Medical University	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Binzhou Medical University Hospital	BinZhou	Shandong
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	The Third Xiang Ya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Heping Hospital Affiliated to Changzhi Medical College	Changzhi	Shanxi
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chifeng Municipal Hospital	Chifeng	Inner Mongolia
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	Chongqing University Three Gorges Hospital	Chongqing	Chongqing
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Mengchao Hepatobiliary Hospital of Fujian Medical	Fuzhou	Fujian
China	Ganzhou People's Hospital	Ganzhou	Jiangxi
China	Guangdong People's Hospital	Guangzhou	Guangdong
China	The Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Guizhou Provincial People'S Hospital	Guiyang	Guizhou
China	The Affiliated Cancer Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Hainan Provincial People's Hospital	Haikou	Hainan
China	The Second Affiliated Hospital of Hainan Medical University	Haikou	Hainan
China	Sir Run Run Shaw Hospital Zhetiang University School of Medicine	Hangzhou	Zhejiang
China	Affiliated Cancer Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Shandong Cancer Hospital	Jinan	Shandong
China	The First Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	Gansu Provincial Cancer Hospital	Lanzhou	Gansu
China	Gansu Provincial Hospital	Lanzhou	Gansu
China	Lanzhou University First Hospital	Lanzhou	Gansu
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Affiliated Hospital of Southwest Medical University	Luzhou	Sichuan
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Affiliated Hospital Of North Sichuan Medical College	Nanchong	Sichuan
China	Jiangsu Province People's Hospital	Nanjing	Jiangsu
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Ningbo Medical Center Lihuili Hospital	Ningbo	Zhejiang
China	The First Affiliated Hospital of Naval Medical University	Shanghai	Shanghai
China	Third Affiliated Hospital of Naval Medical University	Shanghai	Shanghai
China	Shaoxing People's Hospital	Shaoxing	Zhejiang
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The Sixth People's Hospital of Shen Yang	Shenyang	Liaoning
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	Tianjin Cancer Hospital Airport Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Tianjin Third Central Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	First Affiliated Hospital of Xian Jiaotong University	Xi'an	Shanxi
China	The Second Affiliated Hospital of Air Force Medical University	Xi'an	Shanxi
China	Xi'an International Medical Center Hospital	Xi'an	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Affiliated Hospital Of Zunyi Medical University	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-free survival (RFS)	RFS assessed by the Blinded Independent Image Review Committee and the investigator is the time from randomization to the first local, regional recurrence or distant metastasis, or death from any cause, whichever occurred first.	Baseline up to 3 years.
Secondary	Time to recurrence(TTR)	TTR assessed by the Blinded Independent Image Review Committee and the investigator is the time from randomization to the first local, regional recurrence or distant metastasis, whichever occurred first.	Baseline up to 3 years.
Secondary	Time to extrahepatic metastasis or macrovascular invasion	Time to extrahepatic metastasis or macrovascular invasion as assessed by the investigator.	Baseline up to 3 years.
Secondary	Overall survival (OS)	OS defined as the time from the date of randomization until the date of death due to any cause.	Baseline up to 3 years.
Secondary	Objective response rate (ORR) after first recurrence	subjects with evaluable tumor lesion status who were cross-treated with Anlotinib hydrochloride capsules combined with Penpulimab injection developed complete response or partial response after a first HCC relapse as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	Baseline up to 3 years.