A Phase III Clinical Trial of AK105 Injection Combined With Anlotinib Hydrochloride Capsules Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)

Advanced Hepatocellular Carcinoma (HCC) Clinical Trial

Official title:

A Randomized, Controlled, Open-label, Multicenter Phase III Clinical Trial of AK105 Injection Combined With Anlotinib Hydrochloride Capsules Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04344158
• Other study ID #: ALTN-AK105-III-02
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2020
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Jia Fan, Doctor
• Phone: 021-31587861
• Email: fan.jia[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, controlled, open-label, multicenter study to evaluate efficacy of AK105 injection combined with Anlotinib Hydrochloride Capsules versus Sorafenib. Patients are treated with AK105 injection combined with Anlotinib Hydrochloride Capsules or Sorafenib, with 2:1 random ratio. Every 21 days is a treatment cycle.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 648
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 1. 18-75 years old; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy = 3 months.

2. Histopathology or cytology confirmed as HCC. 3. Has not received any systematic treatment for HCC. 4. Stage B or C in the Barcelona Clinic Liver Cancer (BCLC) classification, and is not suitable for surgery or local treatment, or progress after surgery or local treatment.

5. Child-Pugh liver function classification : A or B (=7 points). 6. Central nervous system metastasis has no clinical symptoms or is stable at least 4 weeks after treatment.

7. Quantification of HBV DNA <500IU/ml or 2500 Copys/ml, and anti-HBV therapy should be given for at least 2 weeks before the first administration; Quantification of HCV RNA is positive must complete antiviral therapy at least 1 month before the first administration.

8. Patients who progress after local treatment should be at least 4 weeks after the end of local treatment.

9. Radiotherapy for bone metastases accompanied by clinical symptoms must be completed at least 2 weeks before the first administration.

10. Has at least one measurable lesion. 11. Adequate organ function. 12. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ;No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.

13.Understood and signed an informed consent form.

Exclusion Criteria:

• 1. Histopathology or cytology confirmed as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, hepatobiliary cell carcinoma, mixed liver cancer, etc.

2. Has used anti-angiogenic drugs such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, bevacizumab, or related immunotherapy drugs for PD-1, PD-L1, etc.

3. Has received systemic treatment such as chemotherapy and biological therapy. 4. Has a history of hepatic encephalopathy. 5. According to imaging examination, the portal vein has invasion of cancer embolus, inferior vena cava or heart involvement.

6. Hepatitis B with hepatitis C or hepatitis D infection. 7. Has received or planned to receive organ transplantation. 8. Has other malignant tumors within 5 years. 9. Has multiple factors affecting oral medication. 10. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

11. Has any bleeding or bleeding events =grade 3 in the first 4 weeks before the first administration.

12. Has unhealed wounds, fractures, active gastric and duodenal ulcers, positive continuous fecal occult blood, ulcerative colitis in the first 4 weeks before the first administration.

13. Has adverse events caused by previous therapy except alopecia that did not recover to =grade 1.

14. Has received surgery, or unhealed wounds within 4 weeks before the first administration.

15. Has drug abuse history that unable to abstain from or mental disorders. 16. Has any serious and / or uncontrolled disease. 17. Has received vaccination or attenuated vaccine within 4 weeks prior to the first administration.

18. Has received anti-tumor Traditional Chinese Medicine within 2 weeks before the first administration.

19. Severe hypersensitivity after administration of other monoclonal antibodies.

20. Has any active autoimmune disease or history of autoimmune disease. 21.Immunosuppressant or systemic or absorbable local hormone therapy is required to achieve the aim of immunosuppression (dose > 10mg/ day prednisone or other therapeutic hormones) and is still used within 2 weeks after the first administration.

22.Has participated in other anticancer drug clinical trials within 4 weeks. 23.Portal hypertension with high risk of hemorrhage, or have red sign confirmed by gastroscopy.

24.According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma (HCC)
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• AK105 Injection
AK105 200mg intravenously (IV) on day 1 of each 21-day cycle.
• Anlotinib Hydrochloride Capsules
Anlotinib capsules 10mg given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
• Sorafenib Tosylate Tablets
Sorafenib Tosylate Tablets 400mg given orally, twice daily in 21-day cycle.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Ditan Hospital.Capital Medical University	Beijing	Beijing
China	Beijing Luhe Hospital.Capital Medical University	Beijing	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing	Beijing
China	Beijing YouAn Hospital.Capital Medical University	Beijing	Beijing
China	Chinese Pla General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	Hunan Cancar Hospital	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Affiliated Hospital of Chengdu University	Chengdu	Sichuan
China	West China School of Medical Sichuan University	Chengdu	Sichuan
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancar Center	Guangzhou	Guangdong
China	The First Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou	Hainan
China	Affiliated Tumor Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	Anhui Provincial Hospital	Hefei	Anhui
China	The first hospital of Lanzhou University	Lanzhou	Gansu
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi Zhuang Autonomous Region
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi Zhuang Autonomous Region
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Zhongshan Hospital, Fuadn University	Shanghai	Shanghai
China	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin First Central Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancar institute & Hospital	Tianjin	Tianjin
China	Tianjin Second People's Hospital	Tianjin	Tianjin
China	Tianjin Third Central Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang Uygur Autonomous Region
China	Gansu Wuwei Tumour Hospital	Wuwei	Gansu
China	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Shanxi Provincial Cancer Hospital	Xi'an	Shanxi
China	Tangdu Hospital of the Fourth Military Medical University of the People's Liberation Army of China	Xi'an	Shanxi
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan Province People's Hospital	Zhengzhou	Henan

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	Overall survival (OS)	OS defined as the time from the first dose to death from any cause. Subjects who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.	Up to 96 weeks
Secondary	Progression-free survival (PFS)	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.	Up to 96 weeks
Secondary	Overall response rate(ORR)	Percentage of subjects achieving complete response (CR) and partial response (PR).	Up to 96 weeks
Secondary	Disease control rate(DCR)	Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).	Up to 96 weeks
Secondary	Duration of Response (DOR)	DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.	Up to 96 weeks