Clinical trial NCT04854668: A Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer
Official title: A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-22
Enrollment: 748
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 an open label, randomized, phase Ⅲ study to treat subjects with RAS/BRAF wild-type, unresectable metastatic colorectal cancer. The patients will be randomized into two arms consist of Anlotinib (3 weeks/cycle) + CapeOx and Bevacizumab (3 week/cycle) + CapeOx at a ratio of 1:1. This study is conducted to assess the efficacy and safety of Anlotinib and Chemotherapy as first-line treatment in subjects with RAS/BRAF wild-type Metastatic Colorectal Cancer.


Eligibility criteria: Inclusion Criteria:

* 1. Understood and Signed an informed consent form. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1；Life expectancy≥ 3 months.

  3. Histologically or cytologically confirmed unresectable metastatic colorectal cancer.

  4. Has RAS/BRAF wild-type. 5. Has at least one measurable lesion. 6. Adequate organ function. 7.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.

Exclusion Criteria:

* 1.Has dMMR/MSI-H. 2. Combined with the following diseases or medical history:

  1. Previous or co-existing malignancies within 3 years except for cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors；
  2. Has many factors that affect the oral administration of drugs；
  3. Has Gastrointestinal bleeding or perforation within 4 weeks before the first dose；
  4. Has active inflammatory bowel disease within 4 weeks before the first dose；
  5. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage；
  6. Patients whose adverse events (except hair loss) caused by previous treatment did not recover to ≤CTCAE 1 degree；
  7. Has received major surgical procedure、biopsy or obvious traumatic injury within 28 days before the first dose；
  8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary of blood vessels is unclear；
  9. Has any bleeding event or the level of bleeding events ≥ CTCAE 3；
  10. Has unhealed wounds, ulcerative or fractures；
  11. Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism；
  12. Has a history of psychotropic substance abuse and are unable to quit ；
  13. Has any severe and / or uncontrolled disease； 3.Tumor related symptoms and treatment

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  1. Has received chemotherapy, surgery, radiotherapy, and other anti-cancer therapy within 4 weeks before the first dose.
  2. Has received anti-tumor Chinese patent medicine which were approved by NMPA Within 2 weeks before the first dose.
  3. Previous adjuvant therapy containing anti-vascular or anti-EGFR targeted drugs.
  4. Has received systematic treatment for advanced colorectal cancer.
  5. Has symptomatic brain metastases or control of symptoms \< 2 month. 4.Has participated in other anticancer drug clinical trials within 4 weeks. 5.According to the judgement of the researchers, there are other factors that may lead to the termination of the study.

Primary outcomes:
measure: Progression Free Survival (PFS) assessed by IRC
timeFrame: Baseline up to 15 months
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: Baseline up to 15 months
measure: Overall survival (OS)
timeFrame: Baseline up to 20 months
measure: Objective Response Rate（ORR）
timeFrame: Baseline up to 15 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to 15 months
measure: Duration of Response (DOR)
timeFrame: Baseline up to 15 months
Other outcomes:
Locations:
city: Chizhou
country: China
facility: The People's Hospital of Chizhou
state: Anhui
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Cancer Hospital
state: Anhui
city: Xuancheng
country: China
facility: Xuancheng People's Hospital
state: Anhui
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Frist Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Fuling Hospital Affiliated to Chongqing University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
state: Gansu
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: The First Affiliated Hospital Of Guangzhou Medical University
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Workers' Hospital
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Qinhuangdao
country: China
facility: The First Hospital of Qinhuangdao
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Zhangjiakou
country: China
facility: The First Affiliated Hospital of Hebei North University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Affiliated Cancer Hospital
state: Heilongjiang
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Kaifeng
country: China
facility: Huaihe Hospital of Henan University
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang Second General Hospital
state: Henan
city: Xinyang
country: China
facility: Xinyang 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: Tongji Hospital Affiliated to Tongji Medical College Hust
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Chifeng
country: China
facility: Affiliated Hospital of Chifeng University
state: Inner Mongolia
city: Chifeng
country: China
facility: Chifeng Municipal hospital
state: Inner Mongolia
city: Changzhou
country: China
facility: The First Peoples Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Hospital of C.M.
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province People's Hospital
state: Jiangsu
city: Taizhou
country: China
facility: Jiangsu Taizhou People's Hospital
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou Second People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu Province
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Pingxiang
country: China
facility: JiangXi PingXiang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Province FAW General Hospital
state: Jilin
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Meihekou
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Yanji
country: China
facility: Yanbian University Hospital
state: Jilin
city: Dalian
country: China
facility: The First Affiliatde Hospital of DaLin Medical University
state: Liaoning
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Panjin
country: China
facility: Genertec Liaoyou Gem Flower Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region Cancer Hospital
state: Neimenggu
city: Xining
country: China
facility: Qinghai University Affiliated Hospital
state: Qinghai
city: Hanzhong
country: China
facility: 3201 Hospital
state: Shaanxi
city: Hanzhong
country: China
facility: Hanzhong Central Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital of PLA Air Force Military Medical University
state: Shaanxi
city: Jinan
country: China
facility: Shandong Cancer Hospital Affiliated to Shandong Univercity
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang Hospital of Traditional Chinese Medicine
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Longhua Hospital Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Changzhi
country: China
facility: Changzhi People's Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Tianjin
country: China
facility: Peking University BinHai Hospital
state: Tianjin
city: Kashgar
country: China
facility: The First People's Hospital of Kashgar
state: Xinjiang
city: Ürümqi
country: China
facility: Affiliated Tumor Hospital of Xinjiang Medical University
state: Xinjiang
city: Ürümqi
country: China
facility: First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Huzhou
country: China
facility: Huzhou Cancer Hospital
state: Zhejiang
Study officials:
References: