Clinical trial NCT04344158: A Phase III Clinical Trial of AK105 Injection Combined With Anlotinib Hydrochloride Capsules Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced Hepatocellular Carcinoma (HCC)
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-14
Enrollment: 648
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 \&gt; 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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 96 weeks
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 96 weeks
measure: Overall response rate（ORR）
timeFrame: Up to 96 weeks
measure: Disease control rate（DCR）
timeFrame: Up to 96 weeks
measure: Duration of Response (DOR)
timeFrame: Up to 96 weeks
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Ditan Hospital.Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing YouAn Hospital.Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese Pla General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Luhe Hospital.Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: The first hospital of Lanzhou University
state: Gansu
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Wuwei
country: China
facility: Gansu Wuwei Tumour Hospital
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital，Sun Yat-sen University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi Zhuang Autonomous Region
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi Zhuang Autonomous Region
city: Nanning
country: China
facility: The Second Nanning People's Hospital
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Guiyang
country: China
facility: Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Haikou
country: China
facility: The Second Affiliated Hospital of Hainan Medical Universit
state: Hainan
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Qinhuangdao
country: China
facility: First Hospital Of Qinhuangdao
state: Hebie
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical University
state: Heibei
city: Harbin
country: China
facility: Affiliated Tumor Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang First People's Hospita
state: Henan
city: Sanmenxia
country: China
facility: Sanmenxia Central Hospital
state: Henan
city: Xinxiang
country: China
facility: Xinxiang central hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancar Hospital
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital(Department II of Gastroenterology and Urology/Hepatobiliary Surgery)
state: Hunan
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital Affiliated to Jilin Universit
state: Jilin
city: Changchun
country: China
facility: Jilin Guowen Hospital
state: Jilin
city: Gansu
country: China
facility: Gansu Provincial Hospital
state: Lanzhou
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shenyang
country: China
facility: The Sixth People's Hospital Of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Baoji
country: China
facility: Baoji Central Hospital
state: Shaanxi
city: Hanzhong
country: China
facility: Hanzhong Central Hospital
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng people's Hospital
state: Shandong
city: Weifang
country: China
facility: Yidu Central Hospital Of Weifang
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital, Fuadn University
state: Shanghai
city: Shanghai
country: China
facility: The Third Affiliated Hospital of the Second Military Medical University of the Chinese people's Liberation Army
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provinaial Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: Tangdu Hospital of the Fourth Military Medical University of the People's Liberation Army of China
state: Shanxi
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Xi'an
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Chengdu
country: China
facility: Affiliated Hospital of Chengdu University
state: Sichuan
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancar institute & Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Second People's Hospital
state: Tianjin
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang Uygur Autonomous Region
city: Hangzhou
country: China
facility: Shulan (Hangzhou) hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou People's Hospital
state: Zhejiang
Study officials:
References: