A Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04854668
• Other study ID #: ALTN-?-02
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 30, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2023
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 748
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Anlotinib hydrochloride capsule
Anlotinib hydrochloride capsule 12mg 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);
• Bevacizumab
Bevacizumab 7.5mg/kg, intravenous drip, on Day 1
• Oxaliplatin
Oxaliplatin 130mg/m2, intravenous drip, on Day 1;
• Capecitabine
Capecitabine 850mg/m2 administrated orally twice daily from Day 1-14.

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	China-Japan Friendship Hospital	Beijing	Beijing
China	Peking University Frist Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Jilin Province FAW General Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Changzhi People's Hospital	Changzhi	Shanxi
China	The First Peoples Hospital of Changzhou	Changzhou	Jiangsu
China	Affiliated Hospital of Chifeng University	Chifeng	Inner Mongolia
China	Chifeng Municipal hospital	Chifeng	Inner Mongolia
China	The People's Hospital of Chizhou	Chizhou	Anhui
China	Fuling Hospital Affiliated to Chongqing University	Chongqing	Chongqing
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The First Affiliatde Hospital of DaLin Medical University	Dalian	Liaoning
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Medical University Union Hospital	Fuzhou	Anhui
China	The First Affiliated Hospital Of Guangzhou Medical University	Guangzhou	Guangdong
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	The Affiliated Cancer Hospital of Guizhou Medical University	Guiyang	Guizhou
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	3201 Hospital	Hanzhong	Shaanxi
China	Hanzhong Central Hospital	Hanzhong	Shaanxi
China	Harbin Medical University Affiliated Cancer Hospital	Harbin	Heilongjiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Anhui Cancer Hospital	Hefei	Anhui
China	Anhui Provincial Hospital	Hefei	Anhui
China	Inner Mongolia Autonomous Region Cancer Hospital	Hohhot	Neimenggu
China	Huzhou Cancer Hospital	Huzhou	Zhejiang
China	Shandong Cancer Hospital Affiliated to Shandong Univercity	Jinan	Shandong
China	Affiliated Hospital of Jining Medical University	Jining	Shandong
China	The First Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	Huaihe Hospital of Henan University	Kaifeng	Henan
China	The First People's Hospital of Kashgar	Kashgar	Xinjiang
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Gansu Provincial Cancer Hospital	Lanzhou	Gansu
China	Gansu Provincial Hospital	Lanzhou	Gansu
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Liuzhou Workers' Hospital	Liuzhou	Guangxi
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Meihekou Central Hospital	Meihekou	Jilin
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Cancer hospital	Nanjing	Jiangsu
China	Jiangsu Province People's Hospital	Nanjing	Jiangsu
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Nanjing Hospital of C.M.	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Nanyang Second General Hospital	Nanyang	Henan
China	Genertec Liaoyou Gem Flower Hospital	Panjin	Liaoning
China	JiangXi PingXiang People's Hospital	Pingxiang	Jiangxi
China	Qingyuan People's Hospital	Qingyuan	Guangdong
China	The First Hospital of Qinhuangdao	Qinhuangdao	Hebei
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Longhua Hospital Shanghai University of Traditional Chinese Medicine	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Shanxi Provincial People's Hospital	Taiyuan	Shanxi
China	Jiangsu Taizhou People's Hospital	Taizhou	Jiangsu
China	Taizhou Second People's Hospital	Taizhou	Jiangsu
China	Tangshan People's Hospital	Tangshan	Hebei
China	Peking University BinHai Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Affiliated Tumor Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	Weifang Hospital of Traditional Chinese Medicine	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital Affiliated to Tongji Medical College Hust	Wuhan	Hubei
China	Affiliated Hospital of Jiangnan University	Wuxi	Jiangsu
China	Shaanxi Provincial People's Hospital	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The Second Affiliated Hospital of PLA Air Force Military Medical University	Xi'an	Shaanxi
China	Xi'an International Medical Center Hospital	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	Qinghai University Affiliated Hospital	Xining	Qinghai
China	Xinyang Central Hospital	Xinyang	Henan
China	Xuancheng People's Hospital	Xuancheng	Anhui
China	Subei People's Hospital of Jiangsu Province	Yangzhou	Jiangsu
China	Yanbian University Hospital	Yanji	Jilin
China	Yantai Yuhuangding Hospital	Yantai	Shandong
China	The First Affiliated Hospital of Hebei North University	Zhangjiakou	Hebei
China	Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of ZhengZhou University	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	Progression Free Survival (PFS) assessed by IRC	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.	Baseline up to 15 months
Secondary	Progression free survival (PFS)	PFS defined as the time from first dose until the first documented progressive disease (PD) or death from any cause.	Baseline up to 15 months
Secondary	Overall survival (OS)	OS defined as the time from the first dose to death from any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up.	Baseline up to 20 months
Secondary	Objective Response Rate(ORR)	Percentage of subjects achieving complete response (CR) and partial response (PR) .	Baseline up to 15 months
Secondary	Disease Control Rate (DCR)	Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).	Baseline up to 15 months
Secondary	Duration of Response (DOR)	DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first.	Baseline up to 15 months